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Mazboudi R, Mulhall Maasz H, Resch MD, Wen K, Gottlieb P, Alimova A, Khayat R, Collins ND, Kuschner RA, Galarza JM. A recombinant virus-like particle vaccine against adenovirus-7 induces a potent humoral response. NPJ Vaccines 2023; 8:155. [PMID: 37821505 PMCID: PMC10567840 DOI: 10.1038/s41541-023-00754-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Accepted: 10/02/2023] [Indexed: 10/13/2023] Open
Abstract
Adenoviruses (AdVs) cause infections in humans that range from mild to severe, and can cause outbreaks particularly in close contact settings. Several human AdV types have been identified, which can cause a wide array of clinical manifestations. AdV types 4 and 7 (AdV-4 and AdV-7), which are among the most commonly circulating types in the United States, are known to cause acute respiratory disease that can result in hospitalization and rarely, death. Currently, the only vaccines approved for use in humans are live virus vaccines against AdV-4 and AdV-7, though these vaccines are only authorized for use in U.S. military personnel. While they are efficacious, use of these live virus vaccines carries considerable risks of vaccine-associated viral shedding and recombination. Here, we present an alternative vaccination strategy against AdV-7 using the virus-like particle platform (AdVLP-7). We describe the production of stable recombinant AdVLP-7, and demonstrate that AdVLP-7 is structurally analogous to wild-type AdV-7 virions (WT AdV-7). Preclinical immunogenicity studies in mice show that AdVLP-7 elicits a potent humoral immune response, comparable to that observed in mice immunized with WT AdV-7. Specifically, AdVLP-7 induces high titers of antibodies against AdV-7-specific antigens that can effectively neutralize AdV-7.
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Affiliation(s)
- Ryan Mazboudi
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | | | - Matthew D Resch
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | - Ke Wen
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA
| | - Paul Gottlieb
- CUNY School of Medicine, The City College of New York, New York, NY, 10031, USA
| | - Aleksandra Alimova
- CUNY School of Medicine, The City College of New York, New York, NY, 10031, USA
| | - Reza Khayat
- Department of Chemistry and Biochemistry, The City College of New York, New York, NY, 10031, USA
| | - Natalie D Collins
- Viral Diseases Branch, Walter Reed Army Institute for Research, Silver Spring, MD, 20910, USA
| | - Robert A Kuschner
- Viral Diseases Branch, Walter Reed Army Institute for Research, Silver Spring, MD, 20910, USA
| | - Jose M Galarza
- TechnoVax, Inc., 6 Westchester Plaza, Elmsford, NY, 10523, USA.
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2
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Wu X, Zhang J, Lan W, Quan L, Ou J, Zhao W, Wu J, Woo PCY, Seto D, Zhang Q. Molecular Typing and Rapid Identification of Human Adenoviruses Associated With Respiratory Diseases Using Universal PCR and Sequencing Primers for the Three Major Capsid Genes: Penton Base, Hexon, and Fiber. Front Microbiol 2022; 13:911694. [PMID: 35633710 PMCID: PMC9133664 DOI: 10.3389/fmicb.2022.911694] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Accepted: 04/20/2022] [Indexed: 11/13/2022] Open
Abstract
Human adenoviruses (HAdVs) within species B, C, and E are responsible for highly contagious and potentially severe respiratory disease infections. The traditional method to type these pathogens was based on virus neutralization and hemagglutination assays, which are both time-consuming and difficult, particularly due to the nonavailability of reagents. Subsequent molecular typing based on the partial characterization of the hexon gene and/or the restriction enzyme analysis (REA) of the genomes is inadequate, particularly in identifying recombinants. Here, a rapid, simple, and cost-effective method for molecular typing HAdV respiratory pathogens is presented. This incorporates three pairs of universal PCR primers that target the variable regions of the three major capsid genes, i.e., hexon, penton base, and fiber genes, that span the genome. The protocol enables typing and characterization of genotypes within species B, C, and E, as well as of some genotypes within species D and F. To validate this method, we surveyed 100 children with HAdV-associated acute respiratory infections identified by direct immunofluorescence (Hong Kong; July through October, 2014). Throat swab specimens were collected and analyzed by PCR amplification and sequencing; these sequences were characterized by BLAST. HAdVs were detected in 98 out of 100 (98%) samples, distributing as follows: 74 HAdV-B3 (74%); 10 HAdV-E4 (10%); 7 HAdV-C2 (7%); 2 HAdV-C6 (2%); 1 HAdV-B7 (1%); 1 HAdV-C1 (1%); 2 co-infection (2%); and 1 novel recombinant (1%). This study is the first detailed molecular epidemiological survey of HAdVs in Hong Kong. The developed method allows for the rapid identification of HAdV respiratory pathogens, including recombinants, and bypasses the need for whole genome sequencing for real-time surveillance of circulating adenovirus strains in outbreaks and populations by clinical virologists, public health officials, and epidemiologists.
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Affiliation(s)
- Xiaowei Wu
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jing Zhang
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wendong Lan
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Lulu Quan
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Junxian Ou
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wei Zhao
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
| | - Jianguo Wu
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
| | - Patrick C. Y. Woo
- Department of Microbiology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
| | - Donald Seto
- Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, VA, United States
- Donald Seto,
| | - Qiwei Zhang
- BSL-3 Laboratory, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou, China
- Foshan Institute of Medical Microbiology, Foshan, China
- *Correspondence: Qiwei Zhang,
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Han X, Xu P, Wang H, Mao J, Ye Q. Incident changes in the prevalence of respiratory virus among children during COVID-19 pandemic in Hangzhou, China. J Infect 2022; 84:579-613. [PMID: 35016902 PMCID: PMC8743798 DOI: 10.1016/j.jinf.2022.01.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 12/24/2021] [Accepted: 01/04/2022] [Indexed: 02/04/2023]
Affiliation(s)
- Xiucui Han
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Pengfei Xu
- Clinical Laboratory, Zhejiang Hospital, Hangzhou, China
| | - Hao Wang
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China
| | - Jianhua Mao
- Department of nephrology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou 310052, China.
| | - Qing Ye
- Department of Clinical Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Children's Regional Medical Center, Hangzhou, 310052, China.
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Lynch JP, Kajon AE. Adenovirus: Epidemiology, Global Spread of Novel Types, and Approach to Treatment. Semin Respir Crit Care Med 2021; 42:800-821. [PMID: 34918322 DOI: 10.1055/s-0041-1733802] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The vast majority of cases are self-limited. However, the clinical spectrum is broad and fatalities may occur. Dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 100 genotypes and 52 serotypes of AdV have been identified and classified into seven species designated HAdV-A through -G. Different types display different tissue tropisms that correlate with clinical manifestations of infection. The predominant types circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been done. Cidofovir has been the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States but currently are not available to civilians.
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Affiliation(s)
- Joseph P Lynch
- Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Adriana E Kajon
- Infectious Disease Program, Lovelace Biomedical Research Institute, Albuquerque, New Mexico
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Chaufan C, Dutescu IA, Fekre H, Marzabadi S, Noh KJ. The military as a neglected pathogen transmitter, from the nineteenth century to COVID-19: a systematic review. Glob Health Res Policy 2021; 6:48. [PMID: 34893071 PMCID: PMC8661370 DOI: 10.1186/s41256-021-00232-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Accepted: 11/17/2021] [Indexed: 12/02/2022] Open
Abstract
Background The risk of outbreaks escalating into pandemics has soared with globalization. Therefore, understanding transmission mechanisms of infectious diseases has become critical to formulating global public health policy. This systematic review assessed evidence in the medical and public health literature for the military as a disease vector. Methods We searched 3 electronic databases without temporal restrictions. Two researchers independently extracted study data using a standardized form. Through team discussions, studies were grouped according to their type of transmission mechanism and direct quotes were extracted to generate themes and sub-themes. A content analysis was later performed and frequency distributions for each theme were generated. Results Of 6477 studies, 210 met our inclusion criteria and provided evidence, spanning over two centuries (1810–2020), for the military as a pathogen transmitter, within itself or between it and civilians. Biological mechanisms driving transmission included person-to-person transmission, contaminated food and water, vector-borne, and airborne routes. Contaminated food and/or water were the most common biological transmission route. Social mechanisms facilitating transmission included crowded living spaces, unhygienic conditions, strenuous working, training conditions, absent or inadequate vaccination programs, pressure from military leadership, poor compliance with public health advice, contractor mismanagement, high-risk behaviours, and occupation-specific freedom of movement. Living conditions were the most common social transmission mechanism, with young, low ranking military personnel repeatedly reported as the most affected group. Selected social mechanisms, such as employment-related freedom of movement, were unique to the military as a social institution. While few studies explicitly studied civilian populations, considerably more contained information that implied that civilians were likely impacted by outbreaks described in the military. Conclusions This study identified features of the military that pose a significant threat to global health, especially to civilian health in countries with substantial military presence or underdeveloped health systems. While biological transmission mechanisms are shared by other social groups, selected social transmission mechanisms are unique to the military. As an increasingly interconnected world faces the challenges of COVID-19 and future infectious diseases, the identified features of the military may exacerbate current and similar challenges and impair attempts to implement successful and equitable global public health policies. Supplementary Information The online version contains supplementary material available at 10.1186/s41256-021-00232-0.
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Affiliation(s)
| | | | - Hanah Fekre
- Faculty of Health, York University, Toronto, Canada.
| | | | - K J Noh
- Independent Scholar, Oakland, USA
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Shieh WJ. Human adenovirus infections in pediatric population - an update on clinico-pathologic correlation. Biomed J 2021; 45:38-49. [PMID: 34506970 PMCID: PMC9133246 DOI: 10.1016/j.bj.2021.08.009] [Citation(s) in RCA: 84] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 08/30/2021] [Accepted: 08/30/2021] [Indexed: 01/23/2023] Open
Abstract
Human adenoviruses can cause infections at any age but most commonly in pediatric population, especially in young children and infants. By the time of 10 years old, most children have had at least one episode of adenovirus infection. Adenoviruses can cause many symptoms similar to common cold, including rhinorrhea, fever, cough, and sore throat. Lower respiratory infections such as bronchitis, bronchiolitis, and pneumonia can be severe and even fatal. Other diseases such as conjunctivitis, gastroenteritis, cystitis, myocarditis, cardiomyopathy, and meningoencephalitis can also be associated with adenovirus infections. A variety of recent advancement of structural and molecular biology methods have revamped the taxonomy of adenoviruses and furthered our understanding of the diversity of related clinical diseases. Because of the wide spectrum and complexity of diseases associated with human adenovirus infections, the scope of this review is limited to basic virology and epidemiology of adenoviruses with a main focus on the clinico–pathologic correlation. Clinical manifestations and pathology of any infectious disease are always related; therefore, it is logical to review clinico–pathologic correlation within the specific disease entity caused by adenoviruses to better understand this common viral infection in pediatric population.
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Affiliation(s)
- Wun-Ju Shieh
- Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
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Abstract
Many of us had refresher courses in virology, immunology, and epidemiology in 2020, and we were reminded of the fact that Homo sapiens, the wiliest predator on the planet, has been hunting everything that moves for millennia. These repeated interspecies contacts inherently lead to recurrent zoonosis (nonhuman to human) and anthroponosis (human to nonhuman). Given the accelerating changes in our ecosystems since the neolithic revolution, it was not surprising to see a virus that spreads via aerosolization and liquid droplets cause a pandemic in a few months. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic begs the question-which viruses could cause a global threat? In this Opinion, the characteristics that make adenoviruses a risk, which include efficient intra- and interspecies transmission, thermostable particles, persistent/latent infections in diverse hosts, and the ability to readily recombine and escape herd immunity, are discussed.
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Affiliation(s)
- Eric J. Kremer
- Institut de Génétique Moléculaire de Montpellier, Université de Montpellier, CNRS, Montpellier, France
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8
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Zhang XJ, Zheng JY, Li X, Liang YJ, Zhang ZD. Usefulness of metagenomic next-generation sequencing in adenovirus 7-induced acute respiratory distress syndrome: A case report. World J Clin Cases 2021; 9:6067-6072. [PMID: 34368328 PMCID: PMC8316940 DOI: 10.12998/wjcc.v9.i21.6067] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 04/26/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Direct metagenomic next-generation sequencing (mNGS) of clinical samples is an effective method for the molecular diagnosis of infection. However, its role in the diagnosis of patients with acute respiratory distress syndrome (ARDS) of an unknown infectious etiology remains unclear.
CASE SUMMARY A 33-year-old man was admitted to our center for a cough and febrile sensation. Shortly after admission, the patient was diagnosed with ARDS and treated in the intensive care unit. Subsequently, chest computed tomography features suggested an infection. mNGS was performed and the results were indicative of an infection caused by adenovirus type 7. The patient recovered after receiving appropriate treatment.
CONCLUSION mNGS is a promising tool for the diagnosis of ARDS caused by infectious agents. However, further studies are required to develop strategies for incorporating mNGS into the current diagnostic process for the disease.
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Affiliation(s)
- Xiao-Juan Zhang
- Department of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Jia-Yin Zheng
- Department of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Xin Li
- Department of Infectious Disease, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Ying-Jian Liang
- Department of Intensive Care Unit, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zhi-Dan Zhang
- Department of Infectious Disease, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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9
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Li J, Wei J, Xu Z, Jiang C, Li M, Chen J, Li Y, Yang M, Gu Y, Wang F, Shu Y, Yang Y, Sun L, Liu Y. Cytokine/Chemokine Expression Is Closely Associated Disease Severity of Human Adenovirus Infections in Immunocompetent Adults and Predicts Disease Progression. Front Immunol 2021; 12:691879. [PMID: 34163488 PMCID: PMC8215364 DOI: 10.3389/fimmu.2021.691879] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Accepted: 05/20/2021] [Indexed: 12/12/2022] Open
Abstract
Increasing human Adenovirus (HAdV) infections complicated with acute respiratory distress syndrome (ARDS) even fatal outcome were reported in immunocompetent adolescent and adult patients. Here, we characterized the cytokine/chemokine expression profiles of immunocompetent patients complicated with ARDS during HAdV infection and identified biomarkers for disease severity/progression. Forty-eight cytokines/chemokines in the plasma samples from 19 HAdV-infected immunocompetent adolescent and adult patients (ten complicated with ARDS) were measured and analyzed in combination with clinical indices. Immunocompetent patients with ARDS caused by severe acute respiratory disease coronavirus (SARS-CoV)-2, 2009 pandemic H1N1 (panH1N1) or bacteria were included for comparative analyses. Similar indices of disease course/progression were found in immunocompetent patients with ARDS caused by HAdV, SARS-CoV-2 or panH1N infections, whereas the HAdV-infected group showed a higher prevalence of viremia, as well as increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK). Expression levels of 33 cytokines/chemokines were increased significantly in HAdV-infected patients with ARDS compared with that in healthy controls, and many of them were also significantly higher than those in SARS-CoV-2-infected and panH1N1-infected patients. Expression of interferon (IFN)-γ, interleukin (IL)-1β, hepatocyte growth factor (HGF), monokine induced by IFN-γ (MIG), IL-6, macrophage-colony stimulating factor (M-CSF), IL-10, IL-1α and IL-2Ra was significantly higher in HAdV-infected patients with ARDS than that in those without ARDS, and negatively associated with the ratio of the partial pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2). Analyses of the receiver operating characteristic curve (ROC) showed that expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra could predict the progression of HAdV infection, with the highest area under the curve (AUC) of 0.944 obtained for IL-10. Of note, the AUC value for the combination of IL-10, IFN-γ, and M-CSF reached 1. In conclusion, the "cytokine storm" occurred during HAdV infection in immunocompetent patients, and expression of IL-10, M-CSF, MIG, HGF, IL-1β, IFN-γ and IL-2Ra was closely associated with disease severity and could predict disease progression.
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Affiliation(s)
- Jin Li
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Jinli Wei
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Zhixiang Xu
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Chunmei Jiang
- Department of Infectious Disease, The People’s Hospital of Longhua, Shenzhen, China
| | - Mianhuan Li
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Jie Chen
- Research and Development Department, Guangzhou Sagene Biotech Co., Ltd., Guangzhou, China
| | - Yanjie Li
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Minghui Yang
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Yuchen Gu
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Fuxiang Wang
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Yuelong Shu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Yang Yang
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
| | - Litao Sun
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China
| | - Yingxia Liu
- Shenzhen Key Laboratory of Pathogen and Immunity, National Clinical Research Center for Infectious Disease, State Key Discipline of Infectious Disease, Shenzhen Third People’s Hospital, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, China
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Porto BN, Moraes TJ. The triad: respiratory microbiome - virus - immune response in the pathophysiology of pulmonary viral infections. Expert Rev Respir Med 2021; 15:635-648. [PMID: 33605840 DOI: 10.1080/17476348.2021.1893168] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The longstanding dogma that the healthy lung is sterile has been refuted by recent advances in culture-independent analyses of airway samples. The respiratory microbiome comprises all airway and lung tissue-associated microbes. These micro-organisms occur throughout the upper and lower respiratory tracts, with different populations and distinct burdens at specific sites and can be classified as pathogenic or commensal. AREAS COVERED The majority of studies investigating the respiratory microbiome have focused on bacteria; however, emerging evidence has revealed the composition of the lung virome, the global viral communities present in the lung tissue. In this review, we searched PubMed and used keywords such as airway microbiome. We restricted outputs to English language and did not limit by any dates. We summarize the up-to-date knowledge on how the microbiome interacts with the host immune system and influences the pathogenesis of pulmonary viral infections. EXPERT OPINION The relationship between colonizing microbes and the host is complex and various factors need to be considered in order to appreciate its pathophysiological consequences. Understanding these intricate mechanisms of interaction among the respiratory microbiome, viruses and the immune response may lead to the development of better therapies to treat or prevent respiratory viral infections.
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Affiliation(s)
- Bárbara N Porto
- Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
| | - Theo J Moraes
- Program in Translational Medicine, Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Paediatrics, University of Toronto, Toronto, Ontario, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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11
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Hang J, Kajon AE, Graf PCF, Berry IM, Yang Y, Sanborn MA, Fung CK, Adhikari A, Balansay-Ames MS, Myers CA, Binn LN, Jarman RG, Kuschner RA, Collins ND. Human Adenovirus Type 55 Distribution, Regional Persistence, and Genetic Variability. Emerg Infect Dis 2020; 26:1497-1505. [PMID: 32568062 PMCID: PMC7323512 DOI: 10.3201/eid2607.191707] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Human adenovirus type 55 (HAdV-55) causes acute respiratory disease of variable severity and has become an emergent threat in both civilian and military populations. HAdV-55 infection is endemic to China and South Korea, but data from other regions and time periods are needed for comprehensive assessment of HAdV-55 prevalence from a global perspective. In this study, we subjected HAdV-55 isolates from various countries collected during 1969-2018 to whole-genome sequencing, genomic and proteomic comparison, and phylogenetic analyses. The results show worldwide distribution of HAdV-55; recent strains share a high degree of genomic homogeneity. Distinct strains circulated regionally for several years, suggesting persistent local transmission. Several cases of sporadic introduction of certain strains to other countries were documented. Among the identified amino acid mutations distinguishing HAdV-55 strains, some have potential impact on essential viral functions and may affect infectivity and transmission.
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12
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Nebeluk N, Foster TP. Design, validation and evaluation of a SYBR green-based quantitative PCR array for comprehensive analysis of adenovirus type 5 transcriptional patterns. J Virol Methods 2020; 281:113880. [PMID: 32413477 DOI: 10.1016/j.jviromet.2020.113880] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 04/14/2020] [Accepted: 04/27/2020] [Indexed: 12/13/2022]
Abstract
The adenoviral genome encodes coordinately expressed early and late gene transcriptional units that specify a complex collection of extensively spliced overlapping mRNAs. These complexities confound the generation of compatible, validated and optimized qPCR assays that permit comprehensive evaluation of adenoviral transcription. We have developed and evaluated a compilation of qPCR assays that represent the majority of the human adenovirus 5 (hAdV5) genome and allow for absolute and relative quantification of transcriptional activity. A panel of specific adenovirus gene primer pairs was designed through computational modeling to be compatible under a single reaction condition, precisely amplify spliced transcript products within each gene class, and not result in cellular or viral RNA/DNA background amplification. Primer pairs and reaction conditions were optimized to generate a single amplification product that was specific for its target amplicon with minimal intra-assay variability. The specificity of target amplicons was confirmed by dissociation curve analysis, gel electrophoresis and sequencing. In all, thirty-two primer sets representing specific gene products, as well as, pan early and late gene regions were validated under identical amplification conditions, thereby enabling a comprehensive assessment of adenoviral transcription within a single plate array. In order to generate positive control templates and to facilitate absolute quantification of gene expression, all target amplicons were cloned to create gene target-specific standards. These plasmid amplicon controls demonstrated that the SYBR qPCR assays exhibited optimal amplification efficiencies with a high sensitivity of detection to less than 10 copies and a linear amplification across at least eight orders of magnitude. The effectiveness and utility of the comprehensive adenoviral transcriptional array was assessed by investigating the changes in Ad5Wt gene expression at 72 versus 24 h post infection. Predictably, overall gene expression was globally increased at 72 h post infection; however, levels of E2 and Late transcripts exhibited the greatest increased expression, reflecting their necessity at this time point for genomic replication and virion assembly. Taken together, these data demonstrate that the adenoviral qPCR transcriptional array is a modular, scalable, and cost-effective method to comprehensively and accurately assess hAdV5 gene transcription. This array is broadly applicable to facilitate: adenoviral vector development; assessment of cell complementation of knockout viruses; antiviral mechanism of action evaluation; next-generation sequencing data validation.
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Affiliation(s)
- Nazary Nebeluk
- Department of Microbiology, Immunology, and Parasitology, USA
| | - Timothy P Foster
- Department of Microbiology, Immunology, and Parasitology, USA; Department of Ophthalmology, USA; The Stanley S. Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA; The Louisiana Vaccine Center, New Orleans, LA, 70112, USA.
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Heo JY, Noh JY, Jeong HW, Choe KW, Song JY, Kim WJ, Cheong HJ. Molecular Epidemiology of Human Adenovirus-Associated Febrile Respiratory Illness in Soldiers, South Korea 1. Emerg Infect Dis 2019; 24:1221-1227. [PMID: 29912713 PMCID: PMC6038737 DOI: 10.3201/eid2407.171222] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
During January 2013–April 2014, we subjected nasopharyngeal specimens collected from patients with acute febrile respiratory illness in a military hospital to PCR testing to detect 12 respiratory viruses and sequence a partial hexon gene for human adenovirus (HAdV) molecular typing. We analyzed the epidemiologic characteristics of HAdV infections and compared clinical characteristics of HAdV types. Among the 305 patients with acute febrile respiratory illness, we detected respiratory viruses in 139 (45.6%) patients; HAdV was the most prevalent virus (69 cases). Of the 40 adenoviruses identified based on type, HAdV-55 (29 cases) was the most prevalent, followed by HAdV-4 (9 cases). HAdV-55 was common in patients with pneumonia (odds ratio 2.17; 95% CI 0.48–9.86) and hospitalized patients (odds ratio 5.21; 95% CI 1.06–25.50). In soldiers with HAdV infection in Korea, HAdV-55 was the most prevalent type and might be associated with severe clinical outcomes.
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14
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Yoon HY, Cho HH, Ryu YJ. Adenovirus pneumonia treated with Cidofovir in an immunocompetent high school senior. Respir Med Case Rep 2019; 26:215-218. [PMID: 30733919 PMCID: PMC6354651 DOI: 10.1016/j.rmcr.2019.01.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2018] [Revised: 01/16/2019] [Accepted: 01/16/2019] [Indexed: 11/26/2022] Open
Abstract
Most adenovirus infections are self-limiting in immunocompetent individuals. Here, we report a case of adenovirus pneumonia in a 17-year-old immunocompetent male. He was admitted to our emergency room complaining of a febrile sense, cough, and diarrhea for four days. Crackles in the left lung and a high fever (40.7 °C) were revealed. Initial chest X-ray and computed tomography images showed consolidation in the left lung. We immediately started empirical antibiotic treatment, but his clinical symptoms and pneumonic consolidation in radiography had not improved by hospital day three. Because adenovirus was detected in his sputum using RT-PCR, he was administered Cidofovir. After 24 h of Cidofovir treatment, the symptoms and fever subsided, and the consolidation in his X-ray was significantly reduced by hospital day nine. The early administration of Cidofovir could be beneficial for the treatment of adenovirus infection in immunocompetent patients.
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Affiliation(s)
- Hee-Young Yoon
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Hyun-Hae Cho
- Department of Radiology, Ewha Womans University, College of Medicine, Seoul, Republic of Korea
| | - Yon Ju Ryu
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
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15
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Song J, Lee H, Cho E. Epidemiological Investigation of the Outbreak of Acute Respiratory Infection caused by Adenovirus Type B55 in a Physical Education School in 2017. Infect Chemother 2019; 51:119-129. [PMID: 31270991 PMCID: PMC6609751 DOI: 10.3947/ic.2019.51.2.119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 02/21/2019] [Indexed: 12/23/2022] Open
Abstract
Background On May 19, 2017, the cluster of 6 acute respiratory infections due to adenovirus in the swimming department of a physical education school (School J) was reported to Korea Centers for Disease Control and Prevention. An epidemiological investigation was conducted to identify the transmission route of the infection and to control the outbreak. Materials and Methods A retrospective cohort study (Study 1) was conducted on students and teachers of the athletic departments using the swimming pool, and a prospective surveillance (Study 2) was conducted on all students and teachers of the School J. A case was defined as any student and school personnel who developed more than two of the following symptoms from April 10 to July 2, 2017: fever, sore throat, cough, rhinorrhea, or headache. Relative risks (RRs) were calculated to compare the attack rates according to potential risk factors. Multivariable logistic regression was performed to identify the risk factors for infection in the outbreak. Results 47 cases were identified: 33 (55.9%) cases occurred among 59 students and teachers in Study 1 and 14 (3.9%) among 362 students and school personnel in Study 2. There were 18 laboratory confirmed adenovirus infection cases. The common symptoms were headache (71.7%), fever (69.6%), rhinorrhea (63.0%), sputum (56.5%), and sore throat (54.3%). 23.9% of the cases were accompanied with diarrhea and 19.6% with eye congestion. None of the cases developed pneumonia. 32.6% of the cases were hospitalized. In Study 1, attack rate in the swimming department was higher than that in others (RR: 1.90; 95% confidence interval [CI]: 1.01-3.60). In Study 2, being a member of the shooting department (RR: 20.70; 95% CI: 4.90-87.47) and being a first year high school student (RR: 10.95; 95% CI: 2.90-41.33) were identified as risk factors for the infections. Genetic analyses of the adenoviruses showed 100% identical sequence in homology and confirmed the human adenovirus B55 (HAdV-B55). No adenovirus was detected at examining the water and environment of the swimming pool and dormitory. Conclusion The outbreak is inferred to be occurred via propagated transmission among the students in the same athletic department, while the students with symptoms of respiratory infection continued performing school activities without any restrictions. Infection control measures such as early detection of symptoms of respiratory infection and restriction of group activity are necessary to prevent respiratory infection outbreak in the communal living setting.
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Affiliation(s)
- Jeongsuk Song
- Division of Infectious Disease Control, Korea Centers for Disease control and Prevention, Cheongju, Korea
| | - Hyerim Lee
- Division of Infectious Disease Control, Korea Centers for Disease control and Prevention, Cheongju, Korea
| | - Enhi Cho
- Division of Control for Zoonotic and vector borne Disease, Korea Centers for Disease control and Prevention, Cheongju, Korea.
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16
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Joffe M, Wagner SD, Tang JW. Case report: a fatal case of disseminated adenovirus infection in a non-transplant adult haematology patient. BMC Infect Dis 2018; 18:58. [PMID: 29374466 PMCID: PMC5787257 DOI: 10.1186/s12879-018-2962-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 01/16/2018] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We report a fatal case of disseminated adenovirus infection in a non-transplant haematology adult patient with chronic lymphocytic leukaemia who had completed combination chemoimmunotherapy a few months before developing respiratory symptoms. In such non-transplant patients, monitoring for adenovirus in the blood is not routine. However, with adenoviruses, when there is a more peripheral (i.e. non-blood) site of infection such as the chest, serial adenovirus monitoring in blood for the duration of that illness may be warranted. CASE PRESENTATION This case started with an initial bacterial chest infection that responded to treatment, followed by an adenovirus pneumonitis that disseminated to his blood a week later with levels of up to 92 million adenovirus DNA copies/ml. Despite prompt treatment with cidofovir, his respiratory function continued to deteriorate over the next two weeks and he was moved to intensive care. Intravenous immunoglobulin and ribavirin were subsequently added to his treatment. However, he died soon after this with a final adenovirus load of 20 million copies/ml in his blood. CONCLUSIONS We recommend that even in non-transplant haematology patients, where such patients present with an acute respiratory adenovirus infection, teams should consider checking the blood for adenovirus to check for signs of disseminated infection. The earlier this can be tested, the earlier treatment can be initiated (if adenovirus positive), which may produce more successful clinical outcomes.
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Affiliation(s)
- Michael Joffe
- Department of Haematology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Simon D Wagner
- Department of Haematology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Julian W Tang
- Clinical Microbiology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust, Level 5 Sandringham Building, Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UK. .,Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, UK.
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17
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18
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Hang J, Vento TJ, Norby EA, Jarman RG, Keiser PB, Kuschner RA, Binn LN. Adenovirus type 4 respiratory infections with a concurrent outbreak of coxsackievirus A21 among United States Army Basic Trainees, a retrospective viral etiology study using next-generation sequencing. J Med Virol 2017; 89:1387-1394. [PMID: 28198541 DOI: 10.1002/jmv.24792] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 01/30/2017] [Indexed: 11/09/2022]
Abstract
Human adenoviruses (HAdV), in particular types 4 and 7, frequently cause acute respiratory disease (ARD) during basic military training. HAdV4 and HAdV7 vaccines reduced the ARD risk in U.S. military. It is important to identify other respiratory pathogens and assess their potential impact on military readiness. In 2002, during a period when the HAdV vaccines were not available, throat swabs were taken from trainees (n = 184) with respiratory infections at Fort Jackson, South Carolina. Viral etiology was investigated initially with viral culture and neutralization assay and recently in this study by sequencing the viral isolates. Viral culture and neutralization assays identified 90 HAdV4 isolates and 27 additional cultures that showed viral cytopathic effects (CPE), including some with picornavirus-like CPE. Next-generation sequencing confirmed these results and determined viral genotypes, including 77 HAdV4, 4 HAdV3, 1 HAdV2, 17 coxsackievirus A21 (CAV21), and 1 enterovirus D68. Two samples were positive for both HAdV4 and CAV21. The identified genotypes are phylogenetically close to but distinct from those found during other years or in other military/non-military sites. HAdV4 is the predominant respiratory pathogen in unvaccinated military trainee. HAdV4 has temporal and demographic variability. CAV21 is a significant respiratory pathogen and needs to be evaluated for its current significance in military basic trainees.
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Affiliation(s)
- Jun Hang
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Todd J Vento
- Preventive Medicine Department, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Erica A Norby
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Richard G Jarman
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Paul B Keiser
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Robert A Kuschner
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Leonard N Binn
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
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19
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Yoon BW, Song YG, Lee SH. Severe community-acquired adenovirus pneumonia treated with oral ribavirin: a case report. BMC Res Notes 2017; 10:47. [PMID: 28100279 PMCID: PMC5241922 DOI: 10.1186/s13104-016-2370-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 12/30/2016] [Indexed: 11/16/2022] Open
Abstract
Background Adenovirus is a common pathogen of acute upper respiratory infection in children and is generally self-limiting. Severe adenovirus infections have been reported in immunocompromised hosts especially bone marrow transplantation recipients due to hematologic malignancy. Severe adenovirus pneumonia in immunocompetent hosts has rarely been reported and optimal treatment has not been established. We report a case of community-acquired severe adenovirus pneumonia which was successfully treated with early administration of oral ribavirin. Case presentation A 39 year-old, previously healthy Korean male was admitted with symptoms of cough, myalgia, febrile sensation. Laboratory findings revealed that he had hypoxemia, thrombocytopenia and elevated transaminase. Chest imaging showed a consolidation with pleural effusion, which was rapidly progressed. All microbiological tests were negative except multiplex real-time reverse transcriptase polymerase chain reaction using respiratory specimen, which was positive for human adenovirus. Under the diagnosis of severe adenovirus pneumonia, we started oral ribavirin, which results in complete recovery without any complications. Conclusions This case demonstrates that oral ribavirin, instead of other expensive antiviral treatment, could be a good therapeutic option for the severe adenovirus pneumonia at least occurred in immunocompetent hosts.
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Affiliation(s)
- Byung Woo Yoon
- Department of Internal Medicine, Hanil General Hospital, Seoul, Republic of Korea
| | - Yong Geon Song
- Department of Internal Medicine, Hanil General Hospital, Seoul, Republic of Korea
| | - Seung Hyeun Lee
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea. .,Department of Pulmonary and Critical Care Medicine, Kyung Hee University School of Medicine, Kyungheedae-ro 23, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
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20
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Lynch JP, Kajon AE. Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention. Semin Respir Crit Care Med 2016; 37:586-602. [PMID: 27486739 PMCID: PMC7171713 DOI: 10.1055/s-0036-1584923] [Citation(s) in RCA: 353] [Impact Index Per Article: 39.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians.
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Affiliation(s)
- Joseph P Lynch
- Division of Pulmonary, Critical Care Medicine, Allergy, and Clinical Immunology, Department of Internal Medicine, The David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
| | - Adriana E Kajon
- Department of Infectious Disease, Lovelace Respiratory Research Institute, Albuquerque, New Mexico
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21
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Hoppe E, Pauly M, Robbins M, Gray M, Kujirakwinja D, Nishuli R, Boji Mungu-Akonkwa DD, Leendertz FH, Ehlers B. Phylogenomic evidence for recombination of adenoviruses in wild gorillas. J Gen Virol 2015. [DOI: 10.1099/jgv.0.000250] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Affiliation(s)
- Eileen Hoppe
- Division 12 ‘Measles, Mumps, Rubella and Viruses affecting immunocompromised patients’, Robert Koch Institute, 13353 Berlin, Germany
| | - Maude Pauly
- Division 12 ‘Measles, Mumps, Rubella and Viruses affecting immunocompromised patients’, Robert Koch Institute, 13353 Berlin, Germany
- P3 ‘Epidemiology of highly pathogenic microorganisms’, Robert Koch Institute, 13353 Berlin, Germany
| | - Martha Robbins
- Department of Primatology, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany
| | - Maryke Gray
- Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA
| | - Deo Kujirakwinja
- Wildlife Conservation Society, Grauer's Gorilla Project, Democratic Republic of the Congo
| | - Radar Nishuli
- Institut Congolais pour la Conservation de la Nature, Democratic Republic of the Congo
| | | | - Fabian H. Leendertz
- P3 ‘Epidemiology of highly pathogenic microorganisms’, Robert Koch Institute, 13353 Berlin, Germany
| | - Bernhard Ehlers
- Division 12 ‘Measles, Mumps, Rubella and Viruses affecting immunocompromised patients’, Robert Koch Institute, 13353 Berlin, Germany
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22
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Mölsä M, Hemmilä H, Rönkkö E, Virkki M, Nikkari S, Ziegler T. Molecular characterization of adenoviruses among finnish military conscripts. J Med Virol 2015; 88:571-7. [PMID: 26308159 DOI: 10.1002/jmv.24364] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2015] [Indexed: 11/07/2022]
Abstract
Although adenoviruses were identified as important respiratory pathogens many years ago, little information is available concerning the prevalence of different adenovirus serotypes, which are circulating and causing epidemics in Finnish military training centers. Over a period of five years from 2008 to 2012, 3577 respiratory specimens were collected from military conscripts presenting with symptoms compatible with acute respiratory tract infection. Upon initial testing for certain respiratory viruses by real-time PCR, 837 of these specimens were identified as adenovirus-positive. For 672 of these specimens, the serotype of the adenovirus responsible was successfully determined by DNA sequencing. Serotypes 1, 2, 3, and 4 were detected in 1, 3, 181, and 487 samples, respectively. Adenovirus epidemics were observed during each year of this study. Based on these findings, adenovirus vaccination should be considered for military conscripts in the Finnish Defence Forces.
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Affiliation(s)
- Markos Mölsä
- Centres for Military Medicine and for Biological Threat Preparedness, Helsinki, Finland
| | - Heidi Hemmilä
- Centres for Military Medicine and for Biological Threat Preparedness, Helsinki, Finland
| | - Esa Rönkkö
- National Institute for Health and Welfare (THL), Virology Unit, Helsinki, Finland
| | - Maria Virkki
- Päijät-Häme Social and Health Care Group, Lahti, Finland
| | - Simo Nikkari
- Centres for Military Medicine and for Biological Threat Preparedness, Helsinki, Finland
| | - Thedi Ziegler
- National Institute for Health and Welfare (THL), Virology Unit, Helsinki, Finland.,Research Center for Child Psychiatry, University of Turku, Turku, Finland
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23
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Sanchez JL, Cooper MJ, Myers CA, Cummings JF, Vest KG, Russell KL, Sanchez JL, Hiser MJ, Gaydos CA. Respiratory Infections in the U.S. Military: Recent Experience and Control. Clin Microbiol Rev 2015; 28:743-800. [PMID: 26085551 PMCID: PMC4475643 DOI: 10.1128/cmr.00039-14] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.
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Affiliation(s)
- Jose L Sanchez
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA
| | - Michael J Cooper
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA
| | | | - James F Cummings
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA
| | - Kelly G Vest
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA
| | - Kevin L Russell
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA
| | - Joyce L Sanchez
- Mayo Clinic, Division of General Internal Medicine, Rochester, Minnesota, USA
| | - Michelle J Hiser
- Armed Forces Health Surveillance Center, Silver Spring, Maryland, USA Oak Ridge Institute for Science and Education, Postgraduate Research Participation Program, U.S. Army Public Health Command, Aberdeen Proving Ground, Aberdeen, Maryland, USA
| | - Charlotte A Gaydos
- International STD, Respiratory, and Biothreat Research Laboratory, Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA
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24
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Kajon AE, Hang J, Hawksworth A, Metzgar D, Hage E, Hansen CJ, Kuschner RA, Blair P, Russell KL, Jarman RG. Molecular Epidemiology of Adenovirus Type 21 Respiratory Strains Isolated From US Military Trainees (1996-2014). J Infect Dis 2015; 212:871-80. [PMID: 25748322 DOI: 10.1093/infdis/jiv141] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Accepted: 02/27/2015] [Indexed: 01/21/2023] Open
Abstract
BACKGROUND The circulation of human adenovirus type 21 (HAdV21) in the United States has been documented since the 1960s in association with outbreaks of febrile respiratory illness (FRI) in military boot camps and civilian cases of respiratory disease. METHODS To describe the molecular epidemiology of HAdV21 respiratory infections across the country, 150 clinical respiratory isolates obtained from continuous surveillance of military recruit FRI, and 23 respiratory isolates recovered from pediatric and adult civilian cases of acute respiratory infection were characterized to compile molecular typing data spanning 37 years (1978-2014). RESULTS Restriction enzyme analysis and genomic sequencing identified 2 clusters of closely related genomic variants readily distinguishable from the prototype and designated 21a-like and 21b-like. A-like variants predominated until 1999. A shift to b-like variants was noticeable by 2007 after a 7-year period (2000-2006) of cocirculation of the 2 genome types. US strains are phylogenetically more closely related to European and Asian strains isolated over the last 4 decades than to the Saudi Arabian prototype strain AV-1645 isolated in 1956. CONCLUSIONS Knowledge of circulating HAdV21 variants and their epidemic behavior will be of significant value to local and global FRI surveillance efforts.
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Affiliation(s)
- Adriana E Kajon
- Lovelace Respiratory Research Institute, Albuquerque, New Mexico
| | - Jun Hang
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Anthony Hawksworth
- Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California
| | - David Metzgar
- Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California
| | - Elias Hage
- Institute of Virology, Hannover Medical School, Germany
| | - Christian J Hansen
- Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California
| | - Robert A Kuschner
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
| | - Patrick Blair
- Operational Infectious Diseases Department, Naval Health Research Center, San Diego, California
| | - Kevin L Russell
- Armed Forces Health Surveillance Center, Silver Spring, Maryland
| | - Richard G Jarman
- Viral Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, Maryland
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25
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Retrospective analysis of demographic and clinical factors associated with etiology of febrile respiratory illness among US military basic trainees. BMC Infect Dis 2014; 14:576. [PMID: 25475044 PMCID: PMC4264259 DOI: 10.1186/s12879-014-0576-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2014] [Accepted: 10/17/2014] [Indexed: 12/02/2022] Open
Abstract
Background Basic trainees in the US military have historically been vulnerable to respiratory infections. Adenovirus and influenza are the most common etiological agents responsible for febrile respiratory illness (FRI) among trainees and present with similar clinical signs and symptoms. Identifying demographic and clinical factors associated with the primary viral pathogens causing FRI epidemics among trainees will help improve differential diagnosis and allow for appropriate distribution of antiviral medications. The objective of this study was to determine what demographic and clinical factors are associated with influenza and adenovirus among military trainees. Methods Specimens were systematically collected from military trainees meeting FRI case definition (fever ≥38.0°C with either cough or sore throat; or provider-diagnosed pneumonia) at eight basic training centers in the USA. PCR and/or cell culture testing for respiratory pathogens were performed on specimens. Interviewer-administered questionnaires collected information on patient demographic and clinical factors. Polychotomous logistic regression was employed to assess the association between these factors and FRI outcome categories: laboratory-confirmed adenovirus, influenza, or other FRI. Sensitivity, specificity, positive and negative predictive value were calculated for individual predictors and clinical combinations of predictors. Results Among 21,570 FRI cases sampled between 2004 and 2009, 63.6% were laboratory-confirmed adenovirus cases and 6.6% were laboratory-confirmed influenza cases. Subjects were predominantly young men (86.8% men; mean age 20.8 ± 3.8 years) from Fort Jackson (18.8%), Great Lakes (17.1%), Fort Leonard Wood (16.3%), Marine Corps Recruit Depot (MCRD) San Diego (19.0%), Fort Benning (13.3%), Lackland (7.5%), MCRD Parris Island (8.7%), and Cape May (3.2%). The best multivariate predictors of adenovirus were the combination of sore throat (odds ratio [OR], 2.94; 95% confidence interval [CI], 2.66-3.25), cough (OR, 2.33; 95% CI, 2.11-2.57), and fever (OR, 2.07; 95% CI, 1.90-2.26) with a PPV of 77% (p ≤.05). A combination of cough, fever, training week 0-2 and acute onset were most predictive of influenza (PPV =38%; p ≤ .05). Conclusions Specific demographic and clinical factors were associated with laboratory-confirmed influenza and adenovirus among military trainees. Findings from this study can guide clinicians in the diagnosis and treatment of military trainees presenting with FRI. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0576-2) contains supplementary material, which is available to authorized users.
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Yu B, Dong J, Wang C, Wang Z, Gao L, Zhang H, Wu J, Kong W, Yu X. Trimeric knob protein specifically distinguishes neutralizing antibodies to different human adenovirus species: potential application for adenovirus seroepidemiology. J Gen Virol 2014; 95:1564-1573. [PMID: 24764358 DOI: 10.1099/vir.0.064832-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Adenoviruses (Ads) are non-enveloped DNA viruses that have been extensively studied and used as vectors for gene therapy and several potential vaccines. There are 57 Ad serotypes in seven species (A-G), and Ad neutralizing antibody (NAb) titres can vary by serotype and geographical location. Until now serotype- and species-specific antibodies have been detected by neutralization or haemagglutination inhibition assays. These expensive and cumbersome methods of adenovirus typing have mainly been used in epidemiological studies. Our prior work demonstrated that NAbs against the fiber protein are commonly generated during natural Ad infection in humans and the trimeric knob is preferentially recognized by fiber-induced NAbs. In this study, we expressed nine trimeric knob proteins from representative Ad serotypes of human Ad (HAdV)-A-F in Escherichia coli and found no cross-reactivity of these recombinant proteins with rabbit hyperimmune sera (among HAdV-A-F or within HAdV-C). Results of the ELISA based on Ad2 and Ad5 (both HAdV-C) knob proteins were consistent with those of neutralization assays, indicating that the trimeric knob protein would be a good candidate antigen for detecting Ad serotype-specific NAbs in sera from naturally infected subjects. We also demonstrated the primary seroepidemiology of nine Ad serotypes in 274 children using the knob-based ELISA. These results have potential implications for epidemiology of Ad serotypes and future development of Ad-based vaccines and gene therapy.
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Affiliation(s)
- Bin Yu
- Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, PR China.,National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Jianing Dong
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Chu Wang
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Zhen Wang
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Lei Gao
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Haihong Zhang
- Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, PR China.,National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Jiaxin Wu
- Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, PR China.,National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Wei Kong
- Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, PR China.,National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
| | - Xianghui Yu
- Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, School of Life Sciences, Jilin University, Changchun, PR China.,National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, PR China
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Yun HC, Fugate WH, Murray CK, Cropper TL, Lott L, McDonald JM. Pandemic influenza virus 2009 H1N1 and adenovirus in a high risk population of young adults: epidemiology, comparison of clinical presentations, and coinfection. PLoS One 2014; 9:e85094. [PMID: 24416345 PMCID: PMC3885690 DOI: 10.1371/journal.pone.0085094] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2013] [Accepted: 11/22/2013] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND In 2009, pandemic H1N1 influenza virus (2009 H1N1) emerged worldwide, causing morbidity and mortality that disproportionately affected young adults. Upper respiratory infection (URI), largely due to adenovirus, is an endemic cause of morbidity in military training. Whether clinical presentations differ or excess morbidity results from coinfection is unclear. METHODS The Center for Advanced Molecular Detection evaluates epidemiology and rapid diagnostics of respiratory pathogens in trainees with URI. From May 1, 2009, to November 30, 2009, demographic, clinical, and PCR data from throat and nasal specimens for adenovirus and 2009 H1N1 were prospectively collected. RESULTS 375 trainees with URI enrolled and were tested for both adenovirus and 2009 H1N1 by PCR (median age 20; 89% male). Adenovirus PCR was positive in 72% (96% serotype E-4) and 2009 H1N1 in 20%. Males were more likely to have adenovirus and females more likely to have 2009 H1N1 (p = 0.047). Subjects with 2009 H1N1 presented an average of 1 week earlier in training, had shorter illness duration before enrollment, less sore throat, diarrhea, and fewer abnormal findings on throat exam. Coryza and cough were more common with 2009 H1N1 compared to adenovirus. Subjects with 2009 H1N1 were less likely to have adenovirus than those without, despite persistently high frequencies of adenovirus detections during peak 2009 H1N1 weeks (15% vs. 83%, p < 0.01). Coinfection with adenovirus and 2009 H1N1 was rare (4%). Rates of hospitalization and pneumonia did not differ between the adenovirus, 2009 H1N1, or coinfected groups. CONCLUSION Military trainees with 2009 H1N1 vs. adenovirus have differing clinical presentations, and males are more likely to have adenovirus. Despite high frequencies of adenovirus infection, coinfection with adenovirus and 2009 H1N1 is rare and apparently does not result in increased morbidity.
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Affiliation(s)
- Heather C. Yun
- San Antonio Military Medical Center, Joint Base San Antonio Fort Sam Houston, Texas, United States of America
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America
- * E-mail:
| | - William H. Fugate
- Center for Advanced Molecular Detection, 59th MDW/ST, Joint Base San Antonio-Lackland, Texas, United States of America
| | - Clinton K. Murray
- San Antonio Military Medical Center, Joint Base San Antonio Fort Sam Houston, Texas, United States of America
- Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America
| | - Thomas L. Cropper
- Trainee Health Surveillance, Joint Base San Antonio-Lackland, Texas, United States of America
| | - Lisa Lott
- Center for Advanced Molecular Detection, 59th MDW/ST, Joint Base San Antonio-Lackland, Texas, United States of America
| | - J. Matthew McDonald
- Center for Advanced Molecular Detection, 59th MDW/ST, Joint Base San Antonio-Lackland, Texas, United States of America
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Yu B, Dong J, Wang C, Zhan Y, Zhang H, Wu J, Kong W, Yu X. Characteristics of neutralizing antibodies to adenovirus capsid proteins in human and animal sera. Virology 2013; 437:118-23. [DOI: 10.1016/j.virol.2012.12.014] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Revised: 10/29/2012] [Accepted: 12/28/2012] [Indexed: 11/30/2022]
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Cesario TC. Viruses associated with pneumonia in adults. Clin Infect Dis 2012; 55:107-13. [PMID: 22423119 PMCID: PMC7107903 DOI: 10.1093/cid/cis297] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2011] [Accepted: 02/24/2012] [Indexed: 02/06/2023] Open
Abstract
Viral pneumonia, which is typically associated with disease in childhood, is increasingly recognized as causing problems in adults. Certain viruses, such as influenza virus, can attack fully immunocompetent adults, but many viruses take advantage of more-vulnerable patients. The latter include patients receiving immunosuppressive therapy and elderly subjects, particularly those residing in long-term care facilities. The range of viruses producing pneumonia in adults includes common agents, such as varicella-zoster virus and influenza virus, as well as respiratory syncytial virus, human metapneumovirus, adenoviruses, picornaviruses, and coronaviruses. The roles played by other agents, such as rhinoviruses and human bocaviruses, in pneumonia are still under study. While therapy for most of theses agents, at least in adults, has not yet been fully clarified, it is reasonable to assume antivirals may work in certain situations if they are introduced early enough in the course of infection.
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White DW, Feigley CE, McKeown RE, Hout JJ, Hebert JR. Association between barracks type and acute respiratory infection in a gender integrated Army basic combat training population. Mil Med 2011; 176:909-14. [PMID: 21882781 DOI: 10.7205/milmed-d-10-00418] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Acute respiratory infections (ARIs) are the leading cause of acute morbidity and lost work time in the United States. Few studies have looked at building design and transmission of ARIs. OBJECTIVES This study explores the association of ventilation design, room occupancy numbers, and training week with ARI rates in Army Basic Combat Training barracks. METHODS This observational study captured the overall incidence of ARI in a cohort of 16,258 individuals attending basic combat training at Fort Jackson, South Carolina. RESULTS ARI risk was higher among trainees living in the 60-person room barracks compared with those living in 8-person rooms, which increased rapidly for the first few weeks of training and then declined to baseline. CONCLUSIONS Findings support direct contact as primary ARI transmission mode in this study population based on observed lower ARI risk in smaller room barracks and similar risk in large room barracks despite heating, ventilation, and air conditioning system variability.
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Affiliation(s)
- Duvel W White
- Division of Occupational and Environmental Science, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA
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Clark TW, Fleet DH, Wiselka MJ. Severe community-acquired adenovirus pneumonia in an immunocompetent 44-year-old woman: a case report and review of the literature. J Med Case Rep 2011; 5:259. [PMID: 21718493 PMCID: PMC3148995 DOI: 10.1186/1752-1947-5-259] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2010] [Accepted: 06/30/2011] [Indexed: 11/10/2022] Open
Abstract
INTRODUCTION This case report describes a rare condition: community-acquired adenovirus pneumonia in an immunocompetent adult. The diagnosis was achieved by using a multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay and highlights the usefulness of these novel molecular diagnostic techniques in patients hospitalized with acute respiratory illness. We also performed a literature search for previously published cases and present a summary of the clinical, laboratory and radiological features of this condition. CASE PRESENTATION A 44-year-old immunocompetent Caucasian woman was admitted to our hospital with an acute febrile respiratory illness associated with a rash. Her blood tests were non-specifically abnormal, and tests for bacterial pathogens were negative. Her condition rapidly deteriorated while she was in our hospital and required mechanical ventilation and inotropic support. A multiplex real-time RT-PCR assay performed on respiratory specimens to detect respiratory viruses was negative for influenza but positive for adenovirus DNA. The patient recovered on supportive treatment, and antibiotics were stopped after 5 days. CONCLUSIONS Community-acquired adenovirus pneumonia in immunocompetent adult civilians presents as a non-specific acute febrile respiratory illness followed by the abrupt onset of respiratory failure, often requiring mechanical ventilation. Its laboratory and radiological features are typical of viral infections but also are non-specific. Novel multiplex real-time RT-PCR testing for respiratory viruses enabled us to rapidly make the diagnosis in this case. The new technology could be used more widely in patients with acute respiratory illness and has potential utility for rationalization of the use of antibiotics and improving infection control measures.
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Affiliation(s)
- Tristan W Clark
- Department of Infectious Diseases, Leicester Royal Infirmary, Level 6 Windsor Building, Leicester, LE1 5WW, UK.
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Vento TJ, Prakash V, Murray CK, Brosch LC, Tchandja JB, Cogburn C, Yun HC. Pneumonia in military trainees: a comparison study based on adenovirus serotype 14 infection. J Infect Dis 2011; 203:1388-95. [PMID: 21502080 DOI: 10.1093/infdis/jir040] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Adenovirus serotype 14 (Ad-14) recently emerged as a respiratory pathogen in the United States, with studies suggesting higher morbidity and mortality. This study was conducted to determine whether Ad-14 is associated with clinical outcomes in otherwise healthy patients with pneumonia. METHODS Medical records of military trainees hospitalized with pneumonia during an outbreak of Ad-14 infection were reviewed. Clinical, radiographic, and laboratory parameters were compared on the basis of Ad-14 infection. RESULTS Two hundred thirty-four trainees received a diagnosis of pneumonia, and 83(35%) were hospitalized. Sixty-one percent of patients with pneumonia were Ad-14 positive; 43% of patients with Ad-14 pneumonia were hospitalized (83% of female patients and 40% of male patients; P = .04), compared with 40% of patients with Ad-14 negative cases. Ad-14 infection was associated with higher admission temperature (38.3°C [interquartile range, (IQR) 37.7, 39.4] vs 37.3°C [IQR (36.7, 38.5)]; P < .01) and lower white blood cell count (8.3 × 1000 cells/μL [IQR, 5.7, 12.4] vs 13 × 1000 cells/μL [IQR, 7.5, 12.9]; P = .01), neutrophil count (6.7 × 1000 cells/μL [IQR, 2.8, 9.7] vs 9.7 × 1000 cells/μL [IQR, 5.6, 12.1]; P = .02), lymphocyte count (0.9 × 1000 cells/μL [IQR, 0.8, 1.1] vs 1.3 × 1000 cells/μL [IQR, 1, 1.9]; P = .001), and platelet count (210 × 1000 cells/μL [IQR, 145, 285] vs 261 × 1000 cells/μL [IQR, 238, 343]; P < .01). Ad-14 pneumonia was not associated with specific radiographic findings, pneumonia severity score, intensive care unit admission, longer hospitalization, or 30-day mortality. CONCLUSIONS During an outbreak of Ad-14 infection, Ad-14 infection was not associated with excess overall morbidity or mortality. Ad-14 infection was associated with specific laboratory and clinical parameters and higher hospitalization rates in female trainees. These data provide new insight to the epidemiology of Ad-14 infection.
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Affiliation(s)
- Todd J Vento
- Infectious Diseases Service, Department of Medicine, Brooke Army Medical Center, Fort Sam Houston, TX 78234, USA.
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Khadadah M, Essa S, Higazi Z, Behbehani N, Al-Nakib W. Respiratory syncytial virus and human rhinoviruses are the major causes of severe lower respiratory tract infections in Kuwait. J Med Virol 2010; 82:1462-7. [PMID: 20572084 PMCID: PMC7166574 DOI: 10.1002/jmv.21823] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Respiratory infections are very common in Kuwait, yet little is known about the cause of severe lower respiratory tract infections. This study was designed to investigate the viral cause of lower respiratory tract infections using sensitive molecular methods. PCR was applied to investigate 10 respiratory viruses in respiratory samples from 1,014 patients aged between 3 days to 76 years with acute lower respiratory tract infections. Of the 1,014 patients with lower respiratory tract infections, 288 (28.4%) had a viral infection. One hundred fifty‐five (53.8%) presented with bronchiolitis, 100 (43.7%) with pneumonia, and 33 (11.5%) with croup. One hundred six (36.8%) and 99 (34.4%) patients had evidence of respiratory syncytial virus and human rhinoviruses infections, respectively. Adenoviruses were detected in 44 (15.2%) patients, while influenza A virus in 21 (7.3%) patients. The majority of respiratory syncytial virus infections (84%) were among patients aged <1 year. Similarly, of the 99 patients infected by human rhinoviruses, 50 (50.5%) were also among this age group. In contrast, most of influenza A virus infections, 12 of 21 (57.1%), were among patients aged over 16 years. Parainfluenza virus‐2 and human coronaviruses were not detected in any of the patients' samples. Over the 3‐year period, most of the hospitalized patients were seen during the autumn and winter months from October through March. These data show that respiratory syncytial virus and human rhinoviruses may be the major causes of lower respiratory tract infections in children admitted to hospital in Kuwait. J. Med. Virol. 82:1462–1467, 2010. © 2010 Wiley‐Liss, Inc.
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Affiliation(s)
- M Khadadah
- Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait
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Multiplexed Luminex xMAP assay for detection and identification of five adenovirus serotypes associated with epidemics of respiratory disease in adults. J Clin Microbiol 2010; 48:2217-22. [PMID: 20410343 DOI: 10.1128/jcm.00029-10] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Several serotypes of human adenovirus (HAdV) cause acute respiratory disease (ARD) among healthy adults, sometimes generating broad outbreaks with high attack rates and occasional fatalities. Timely serotype identification provides valuable epidemiological information and significantly contributes to prevention (vaccination) strategies. The prevalence of specific serotypes causing ARD varies geographically. HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 are the serotypes most commonly found in adult populations in the Western Hemisphere. Unfortunately, conventional serotype identification is a tedious process which can take a week or longer. For this reason, new molecular methods for serotype identification are needed. Commercially available rapid antigen and PCR assays for the detection of HAdV are universal but do not distinguish between the different serotypes. We describe the development of a sensitive and specific multiplex assay capable of identifying serotypes 3, 4, 7, 14, and 21. Two sets of primers were used for nonspecific (universal) PCR amplification, and serotype-specific probes coupled to Luminex tags were used for target-specific extension (TSE). PCR and TSE primers were designed using known hexon gene sequences of HAdV. The TSE products of HAdV-3, HAdV-4, HAdV-7, HAdV-14, and HAdV-21 were correctly identified using the Luminex xMAP fluid microsphere-based array system. No cross-reactivity with other respiratory pathogens or other HAdV serotypes was observed. This multiplexed assay can be expanded to include more serotypes and will allow broad and rapid detection and identification of adenoviral serotypes in a high-throughput environment.
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Outbreak of febrile respiratory illness associated with adenovirus 11a infection in a Singapore military training cAMP. J Clin Microbiol 2010; 48:1438-41. [PMID: 20129957 DOI: 10.1128/jcm.01928-09] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Outbreak cases of acute respiratory disease (ARD) associated with subspecies B2 human adenovirus 11a (HAdV-11a) infection were detected during 2005 in a military basic training camp in Singapore. The Singapore HAdV-11a strain is highly similar to other Asian strains of HAdV-11, including strain QS-DLL, which is responsible for the recently described 2006 outbreak of ARD in China.
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Naghipour M, Hart CA, Dove W, Leatherbarrow AJH, Cuevas LE. Adenovirus infections within a family cohort in Iran. Pediatr Pulmonol 2009; 44:749-53. [PMID: 19598232 DOI: 10.1002/ppul.20785] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Adenovirus is one of the most frequent viruses associated with acute respiratory infections (ARI). There is limited information of its transmission within the community. METHODS Cohorts of 50 families with > or =two children were visited weekly for 2 months to ascertain the presence ARI in Rasht, Iran. Nasopharyngeal swabs were obtained from symptomatic participants and at 3-4-day intervals to assess the duration of adenovirus shedding. Adenoviruses were identified by PCR and adenovirus positive amplicons were subjected to DNA sequencing. RESULTS Thirty-three (35%) of 94 ARI episodes in children and 8 (27%) of 30 episodes in adults were due to adenovirus (not significant, NS). 25/50 (50%) families had adenovirus infections. Children had more infections than adults, were more likely to develop symptoms if there was a symptomatic case within the household and episodes had a longer duration (P < 0.05). Adenoviruses were recovered for a median of 11 (interquartile range 5-26) days of follow up in children and 7 (2-20) days in adults (NS). Adenovirus-7 was the most frequent serotype (12 families), followed by adenovirus-6 (5 families), adenovirus-1 and 2 (4 families each), and adenovirus-5 (3 families). Both adenovirus-5 and 7 amplicons fell into two clusters. No mutations were observed during transmission within a family. CONCLUSION A substantial proportion of ARI in the community are due to adenovirus with further transmission within the family. Children > or =2 years experienced a higher proportion of infections than younger children and adults. Viral shedding was more prolonged in children and adenovirus-7 and 5 predominated with several clusters co-circulating in the same season.
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Broderick MP, Hansen CJ, Russell KL. Exploration of the effectiveness of social distancing on respiratory pathogen transmission implicates environmental contributions. J Infect Dis 2009; 198:1420-6. [PMID: 18823270 PMCID: PMC7109839 DOI: 10.1086/592711] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
Background. In both military and civilian settings, transmission of respiratory pathogens may be due to person-to-person and environmental contributions. This possibility was explored in a military training setting, where rates of febrile respiratory illness (FRI) often reach epidemic levels. Methods. Population size and FRI rates were monitored over 10 months in the units of 50–90 individuals. Some units were open to the influx of potentially infectious convalescents (hereafter referred to as “open units,” and some were closed to such an influx (hereafter referred to as “closed units”). Virologic testing and polymerase chain reaction analysis were used to detect adenovirus on surface structures. Results. The odds ratio (OR) associated with FRI in closed units, compared with open units, was 1.13 (95% confidence interval [CI], 0.99–1.28). The OR in units with a population greater than the median size, compared with units with a population lower than the median size was 1.38 (95% CI, 1.23–1.55). Between 5% and 9% of surface samples obtained from selected units harbored viable adenovirus. Conclusions. FRI rates were not reduced in units that were closed to potentially contagious individuals. These findings imply that the primary source of the pathogen is likely environmental rather than human, and they underscore what is known about other virus types. Diligence in identifying the relative roles of different transmission routes is suggested for civilian settings similar to those described in the current study.
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Affiliation(s)
- Michael P Broderick
- Department of Respiratory Disease Research, Naval Health Research Center, San Diego, CA 92106, USA.
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INFLUENZA AND VIRAL RESPIRATORY INFECTIONS. PHARMACOLOGY AND THERAPEUTICS 2009. [PMCID: PMC7332234 DOI: 10.1016/b978-1-4160-3291-5.50081-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Abstract
SUMMARY The number of patients with acquired immunodeficiency has grown steadily as a result of both a larger number of patients receiving solid organ and hematopoietic stem cell transplants and their longer survival times. The use of newer, more potent immunosuppressive regimens has increased the frequency of severe adenovirus infections. Human adenoviruses are a large group of viruses, represented by at least 52 serotypes with various genotypes divided into genomic clusters, and these may cause a broad variety of clinical manifestations. The development of molecular methods has increased the sensitivity and rapidity of adenovirus infection diagnosis. The implementation of PCR assays has significantly contributed to the identification of patients with disseminated adenovirus disease. More recently, the development of real-time PCR assays has permitted virus quantification and patient follow-up. There is no treatment for adenovirus with demonstrated efficacy, although cidofovir is widely used. Sensitive diagnostic tests for adenovirus can contribute to the early diagnosis and successful treatment of life-threatening adenovirus infections, especially in complex immunocompromised patients. The development of improved adenovirus therapy still remains a challenge. Adenovirus genetic diversity should be considered for diagnosis, typing, and therapeutic interventions.
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Lyons A, Longfield J, Kuschner R, Straight T, Binn L, Seriwatana J, Reitstetter R, Froh IB, Craft D, McNabb K, Russell K, Metzgar D, Liss A, Sun X, Towle A, Sun W. A double-blind, placebo-controlled study of the safety and immunogenicity of live, oral type 4 and type 7 adenovirus vaccines in adults. Vaccine 2008; 26:2890-8. [PMID: 18448211 DOI: 10.1016/j.vaccine.2008.03.037] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2007] [Revised: 03/14/2008] [Accepted: 03/20/2008] [Indexed: 11/26/2022]
Abstract
Adenovirus serotypes 4 (ADV-4) and 7 (ADV-7) are important causes of febrile acute respiratory disease (ARD) in US military recruits. Previously licensed vaccines, which effectively controlled adenovirus-associated ARD, are no longer available. In the Fall of 2004 we conducted this Phase 1 randomized, double-blind, placebo-controlled trial of the live, oral ADV-4 and ADV-7 vaccines made by a new manufacturer to assess their safety and immunogenicity. The adenovirus vaccines were administered orally together in a single dose to thirty subjects. Twenty eight additional subjects received placebo. Subjects were then observed for 8 weeks. The most commonly reported adverse events were nasal congestion (33%), cough (33%), sore throat (27%), headache (20%), abdominal pain (17%), arthralgia (13%), nausea (13%) and diarrhea (13%). None of these rates differed significantly from placebo. The duration of vaccine virus fecal shedding was 7-21 days. Seventy three percent of vaccine recipients seroconverted to ADV-4 (GMT 23.3) while 63% seroconverted to ADV-7 (GMT 51.1) by Day 28. The new ADV-4 and ADV-7 vaccines were safe and induced a good immune response in the study population. Expanded trials for safety and efficacy are in progress.
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Affiliation(s)
- Arthur Lyons
- Department of Virus Diseases, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
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43
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Miakotina OL, McCoy DM, Shi L, Look DC, Mallampalli RK. Human adenovirus modulates surfactant phospholipid trafficking. Traffic 2007; 8:1765-1777. [PMID: 17897321 DOI: 10.1111/j.1600-0854.2007.00641.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Surfactant, highly enriched with phosphatidylcholine (PC), is secreted into the airspace by a classic apical secretory route, thereby maintaining lung stability. Herein, we show that adenoviral infection decreases surfactant PC in lungs by inhibiting its apical secretion and redirecting its export in alveolar cells by a basolateral route. These effects were not observed with replication-deficient adenovirus (Ad), specifically lacking early region 1 (E1) gene products. Adenoviral stimulation of basolateral PC export from cells was not observed after pharmacologic inhibition of ATP-binding cassette proteins, after introduction of small interfering RNA to the lipid pump ATP-binding cassette transporter A1 (ABCA1) or in ABCA1-defective human Tangier disease fibroblasts. Adenovirus and its E1A gene product increased ABCA1 levels by transcriptionally activating the ABCA1 gene. Thus, Ad lowers surfactant, in part, by triggering ABCA1-directed basolateral PC export, thereby limiting the cellular pool of surfactant PC destined for apical secretion. The results support a novel pathway, whereby a viral pathogen disrupts surfactant trafficking.
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Affiliation(s)
- Olga L Miakotina
- Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
| | - Diann M McCoy
- Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
| | - Lei Shi
- Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
| | - Dwight C Look
- Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
| | - Rama K Mallampalli
- Department of Internal Medicine, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
- Department of Biochemistry, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
- Department of Veterans Affairs Medical Center, University of Iowa, Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA
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Alesci S, Perera SM, Lai EW, Kukura C, Abu-Asab M, Tsokos M, Morris JC, Pacak K. Adenoviral gene transfer in bovine adrenomedullary and murine pheochromocytoma cells: potential clinical and therapeutic relevance. Endocrinology 2007; 148:3900-7. [PMID: 17525127 PMCID: PMC2527237 DOI: 10.1210/en.2007-0521] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Recombinant adenoviruses (rAd) have been widely used as gene transfer vectors both in the laboratory and in human clinical trials. In the present study, we investigated the effects of adenoviral-mediated gene transfer in primary bovine adrenal chromaffin cells (BACC) and a murine pheochromocytoma cell line (MPC). Cells were infected with one of three nonreplicating E1/E3-deleted (E1(-)/E3(-)) rAd vectors: Ad.GFP, expressing a green fluorescent protein (GFP); Ad.null, expressing no transgene; or Ad.C2.TK, expressing the herpes simplex virus-1 thymidine kinase gene (TK). Forty-eight hours after exposure to Ad.GFP, the percentage of GFP-expressing BACC ranged from 23.5-97% in a dose-dependent manner and similarly from 1.06-84.4% in the MPC, indicating that adrenomedullary cells are a potentially valuable target for adenoviral-mediated gene transfer. Ultrastructural analysis, however, revealed profound changes in the nucleus and mitochondria of cells infected with rAd. Furthermore, infection of BACC with Ad.null was accompanied by a time- and dose-dependent decrease in cell survival due to the vector alone. Specific whole-cell norepinephrine uptake was also decreased in a time- and dose-dependent fashion in BACC. Infection of MPC cells with the Ad.C2.TK vector sensitized them to the cytotoxic effect of the antiviral drug ganciclovir, in direct proportion to the fraction of cells infected with the virus. We conclude that rAd may alter the structural and functional integrity of adrenomedullary cells, potentially interfering with the normal stress response. At the same time, in light of their ability to effectively deliver and express genes in pheochromocytoma cells, they may be applicable to the gene therapy of adrenomedullary tumors.
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Affiliation(s)
- Salvatore Alesci
- Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, USA
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45
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Gray GC. Adenovirus transmission--worthy of our attention. J Infect Dis 2006; 194:871-3. [PMID: 16960772 PMCID: PMC1673215 DOI: 10.1086/507435] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2006] [Accepted: 06/21/2006] [Indexed: 11/03/2022] Open
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46
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Yarovinsky TO, Mohning MP, Bradford MA, Monick MM, Hunninghake GW. Increased sensitivity to staphylococcal enterotoxin B following adenoviral infection. Infect Immun 2005; 73:3375-84. [PMID: 15908364 PMCID: PMC1111844 DOI: 10.1128/iai.73.6.3375-3384.2005] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Staphylococcal enterotoxin B induces toxic shock and is a major virulence factor of staphylococcal diseases. We examined the effects of systemic adenoviral infection on responses to staphylococcal enterotoxin B in a murine model. We found that adenoviral infection markedly increases the severity of liver injury following exposure to staphylococcal enterotoxin B without d-galactosamine sensitization. In adenovirus-infected mice, staphylococcal enterotoxin B triggered a more profound hypothermia and increased apoptosis in the liver. Consistent with these observations, we also found that adenoviral infection primed for an increased production of gamma interferon in vivo and in vitro following stimulation with staphylococcal enterotoxin B. Gamma-interferon-knockout mice did not show increased sensitivity to staphylococcal enterotoxin B following adenoviral infection. These data suggest that a preexisting viral infection primes mice for subsequent staphylococcal enterotoxin B exposure, possibly via a gamma-interferon-mediated mechanism.
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Affiliation(s)
- Timur O Yarovinsky
- Division of Pulmonary, Critical Care, and Occupational Medicine, 100 EMRB, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242, USA.
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47
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Krafft AE, Russell KL, Hawksworth AW, McCall S, Irvine M, Daum LT, Connoly JL, Reid AH, Gaydos JC, Taubenberger JK. Evaluation of PCR testing of ethanol-fixed nasal swab specimens as an augmented surveillance strategy for influenza virus and adenovirus identification. J Clin Microbiol 2005; 43:1768-75. [PMID: 15814997 PMCID: PMC1081350 DOI: 10.1128/jcm.43.4.1768-1775.2005] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2004] [Revised: 10/01/2004] [Accepted: 11/24/2004] [Indexed: 11/20/2022] Open
Abstract
Viral culture isolation has been widely accepted as the "gold standard" for laboratory confirmation of viral infection; however, it requires ultralow temperature specimen storage. Storage of specimens in ethanol at room temperature could expand our ability to conduct active surveillance and retrospective screenings of viruses with rapid and inexpensive real-time PCR tests, including isolates from remote regions where freezing specimens for culture is not feasible. Molecular methods allow for rapid identification of viral pathogens without the need to maintain viability. We hypothesized that ethanol, while inactivating viruses, can preserve DNA and RNA for PCR-based methods. To evaluate the use of ethanol-stored specimens for augmenting surveillance for detection of influenza viruses A and B and adenoviruses (AdV), paired nasal swab specimens were collected from 384 recruits with febrile respiratory illness at Fort Jackson, S.C., in a 2-year study. One swab was stored at ambient temperature in 100% ethanol for up to 6 months, and the other swab was stored at -70 degrees C in viral medium. For viral detection, frozen specimens were cultured for a variety of respiratory viruses, and ethanol-fixed specimens were tested with TaqMan (TM) probe and LightCycler SYBR green (SG) melting curve assays with at least two different PCR targets for each virus. The sensitivities of the TM and SG assays on specimens stored in ethanol for 1 month were 75% and 58% for influenza A, 89% and 67% for influenza B, and 93 to 98% and 57% for AdV, respectively. Lower specificities of the real-time assays corresponded to the increased detection of PCR-positive but culture-negative specimens. Influenza virus RNA was detected as well or better after 6 months of storage in ethanol.
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Affiliation(s)
- A E Krafft
- Department of Molecular Pathology, Armed Forces Institute of Pathology, 1413 Research Blvd., Rockville, MD 20850-3125, USA.
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48
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Aste-Amézaga M, Bett AJ, Wang F, Casimiro DR, Antonello JM, Patel DK, Dell EC, Franlin LL, Dougherty NM, Bennett PS, Perry HC, Davies ME, Shiver JW, Keller PM, Yeager MD. Quantitative adenovirus neutralization assays based on the secreted alkaline phosphatase reporter gene: application in epidemiologic studies and in the design of adenovector vaccines. Hum Gene Ther 2005; 15:293-304. [PMID: 15018738 DOI: 10.1089/104303404322886147] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Replication-defective recombinant adenoviruses (rAd) are used as vectors for vaccines as well as for gene therapy. To determine type-specific antibodies to adenovirus (Ad) serotypes 2, 5, 24, 34, and 35, we developed quantitative neutralization assays using recombinant adenoviruses with the secreted alkaline phosphatase (SEAP) reporter gene. Among the standardized parameters, the concentration of infectious and noninfectious adenoviral particles used in the assay is critical for a reliable comparison of data from different studies. The usefulness of this assay was demonstrated in a pilot epidemiologic study of 40 healthy individuals. In this study, the highest prevalence of antiadenovirus antibodies was found for the Ad2 serotype (82.5%), followed by Ad5 (35%). The prevalence of antiadenovirus antibodies for the serotypes 24, 34, and 35 was low (7.5%, 2.5%, and 0%, respectively). In addition, epidemiologic parameters such as gender and age were statistically evaluated. A positive association was found between age and the presence of anti-Ad5 antibodies. The assay was also useful for evaluating the presence of antiadenovirus antibodies in the design of vaccines using a rhesus monkey model. In this animal model, it was possible to determine differential dose and time responses, and the specificity for the detection of neutralizing antibodies was assessed. The evaluation of serotype-specific neutralizing antibodies can be of both clinical and epidemiologic importance as a means of selecting the appropriate serotype adenovector(s).
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Affiliation(s)
- Miguel Aste-Amézaga
- Department of Virus & Cell Biology, Merck Research Laboratories, Merck & Co., Inc., West Point, PA 19486, USA
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Regagnon C, Souweine B, Archimbaud C, Duperron F, Thouvenot D, Peigue-Lafeuille H. [A fatal case of adenovirus type 3 pneumonia in an immunocompetent adult]. Med Mal Infect 2005; 34:102-4. [PMID: 15620023 DOI: 10.1016/j.medmal.2003.11.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Affiliation(s)
- C Regagnon
- Service de virologie, faculté de médecine, CHU de Clermont-Ferrand, 28, place Henri-Dunant, 63001 Clermont-Ferrand cedex, France
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50
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Faix DJ, Houng HSH, Gaydos JC, Liu SKS, Connors JT, Brown X, Asher LV, Vaughn DW, Binn LN. Evaluation of a rapid quantitative diagnostic test for adenovirus type 4. Clin Infect Dis 2004; 38:391-7. [PMID: 14727210 DOI: 10.1086/380972] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2003] [Accepted: 09/30/2003] [Indexed: 12/17/2022] Open
Abstract
Acute respiratory disease (ARD) due to adenoviruses is a reemerging disease in military recruits. It is a challenge for clinicians to accurately diagnose this disease and to appropriately treat affected individuals. This study investigated the utility of a quantitative, rapid-cycle, real-time fluorogenic polymerase chain reaction (PCR) technique for detecting adenovirus type 4 (Ad4) in a clinical setting. Throat swab specimens and clinical data were collected from US Army basic trainees hospitalized with ARD at Fort Jackson, South Carolina. A total of 140 throat swab specimens were collected from 83 subjects. Rapid PCR results (obtained in <2 h) had a sensitivity of 100% and a specificity of 100%, compared with viral culture. There was no difference, qualitative or quantitative, between frozen and fresh samples for PCR detection of Ad4. Individuals with test results positive for Ad4 were hospitalized longer than were individuals with negative test results. Higher virus loads at hospital admission corresponded to longer lengths of stay for Ad4-positive subjects.
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Affiliation(s)
- Dennis J Faix
- Department of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA
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