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1
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Huang C, Zhang H, Wang J, Li J, Liu Q, Zong Q, Zhang Y, Wang Q, Zhou Q. Preliminary analysis of the role of small hepatitis B surface proteins mutations in the pathogenesis of occult hepatitis B infection via the endoplasmic reticulum stress-induced UPR-ERAD pathway. Open Life Sci 2025; 20:20220951. [PMID: 39926475 PMCID: PMC11806202 DOI: 10.1515/biol-2022-0951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 07/04/2024] [Accepted: 07/30/2024] [Indexed: 02/11/2025] Open
Abstract
A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.
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Affiliation(s)
- Chengrong Huang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
- Department of Clinical Laboratory, Anqing Municipal Hospital, Anqing, 246003, China
| | - Hao Zhang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Jing Wang
- Department of Clinical Laboratory, Nanjing Jiangning Hospital, Nanjing, 211100, China
| | - Jianfei Li
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Qian Liu
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Qiyin Zong
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Yunyun Zhang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Qin Wang
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China
| | - Qiang Zhou
- Department of Clinical Laboratory, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, Hefei, 230601, China
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de Almeida Pondé RA. Detection of hepatitis B virus surface antigen, IgM and IgG antibodies to hepatitis B virus core antigen in the clinical classification and epidemiological surveillance of HBV infection. Mol Biol Rep 2025; 52:195. [PMID: 39903324 DOI: 10.1007/s11033-025-10278-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 01/20/2025] [Indexed: 02/06/2025]
Abstract
Hepatitis B virus surface antigen (HBsAg), IgM and IgG antibodies to hepatitis B virus core antigen (anti-HBcIgM and anti-HBcIgG) comprise serological markers of hepatitis B virus (HBV) infection of great importance in the epidemiological surveillance of hepatitis B, since they have been routinely considered for classifying the acute and chronic clinical forms of HBV infection. This classification is established according to the expression and dynamics of these markers in the infected person's bloodstream, which serves as the basis for the differential diagnosis between the two clinical entities. However, in certain circumstances, both acute and chronic infection, the detection of these markers may not occur in the bloodstream, favoring the occurrence of atypical serological profiles of infection, and compromising the correct infection clinical classification. In addition, the complex and varied nature of hepatitis B serological profiles may compromise the health professional's ability to analyze the case and, thus, correctly classify the infection's clinical form. Since the expression of these markers in the bloodstream occurs dynamically, with consequent changes in the patient's serological profile as he progresses towards recovery or chronicity, the diagnosis of acute or chronic infection may also be compromised, if it is established based on the collection of a single sample and without knowing the patient's clinical history and their epidemiological antecedents. This manuscript addresses the sensitivity and specificity of HBsAg, anti-HBcIgM, and anti-HBcIgG serological markers detection in the clinical classification of HBV infection and in the epidemiological surveillance of hepatitis B. This review is covering the clinical and epidemiological interpretations of the markers in and of themselves, not in reference to any specific assays.
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Affiliation(s)
- Robério Amorim de Almeida Pondé
- Secretaria de Estado da Saúde -SES/Superintendência de Vigilância em Saúde-SUVISA/GO, Gerência de Vigilância Epidemiológica de Doenças Transmissíveis-GVEDT/Coordenação de Análises e Pesquisas-CAP, Goiânia, Goiás, Brazil.
- , Rua 136 Qd F44 Lt 22/24 Ed. César Sebba- Setor Sul, Goiânia, Goiás, 74-093-250, Brazil.
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Gong H, Yao S, Li Y, Chen C, Chen F, Cai C. Combined detection of hepatitis B virus surface antigen and hepatitis B virus DNA using a DNA sensor. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:7319-7324. [PMID: 39364579 DOI: 10.1039/d4ay01629g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/05/2024]
Abstract
Hepatitis B virus (HBV) infection is associated with the progression of liver disease. Occult HBV infection (OBI) is defined as the existence of detectable HBV DNA in HBV surface antigen negative individuals. However, HBV DNA is negative in serum while HBV surface antigen remains positive in incompletely cured chronic HBV infection. Hence, combined detection of HBV surface antigen and HBV DNA is essential for the accurate detection and rehabilitation of HBV infection. Therefore, a multiplex detection strategy based on branched DNA nanostructures was developed. The single-stranded segment of a branched DNA nanostructure (segments of S4 and S2) assembled by four single-stranded DNA was hybridized with the aptamer of HBV surface antigen and DNA hairpin to construct a DNA nanosensor, which can achieve high specificity identification and highly sensitive fluorescence responses to the targets. The detection limits of the developed nanosensor for HBV and HBV DNA are 50 pM and 5 nM, respectively. The combined detection of HBV surface antigen and HBV DNA provides a new insight for more thorough diagnostic evaluation of HBV infection and rehabilitation.
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Affiliation(s)
- Hang Gong
- Yunnan Key Laboratory of Modern Separation Analysis and Substance Transformation, College of Chemistry and Chemical Engineering, Yunnan Normal University, Kunming, 650500, P. R. China.
| | - Shufen Yao
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, China.
| | - Yong Li
- Yunnan Academy of Tobacco Agricultural Sciences, Kunming, 650021, China.
| | - Chunyan Chen
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, China.
| | - Feng Chen
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, China.
| | - Changqun Cai
- Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, China.
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4
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Echevarria-Lima J, Moles R. Monocyte and Macrophage Functions in Oncogenic Viral Infections. Viruses 2024; 16:1612. [PMID: 39459945 PMCID: PMC11512331 DOI: 10.3390/v16101612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/07/2024] [Accepted: 10/08/2024] [Indexed: 10/28/2024] Open
Abstract
Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies.
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Affiliation(s)
- Juliana Echevarria-Lima
- Laboratório de Imunologia Básica e Aplicada, Department of Immunology, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, Brazil;
| | - Ramona Moles
- Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Cancer Center and Research Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA
- Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, USA
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Danpanichkul P, Aboona MB, Sukphutanan B, Kongarin S, Duangsonk K, Ng CH, Muthiah MD, Huang DQ, Seko Y, Díaz LA, Arab JP, Yang JD, Chen VL, Kim D, Noureddin M, Liangpunsakul S, Wijarnpreecha K. Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019. Hepatology 2024; 80:828-843. [PMID: 38598364 DOI: 10.1097/hep.0000000000000872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 02/19/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIMS The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. APPROACH AND RESULTS This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSIONS Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Majd B Aboona
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | | | | | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Cheng Han Ng
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Daniel Q Huang
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- MASLD Research Center, Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, Japan
| | - Luis Antonio Díaz
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Observatorio Multicéntrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vincent L Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Mazen Noureddin
- Houston Research Institute and Houston Methodist Hospital, Houston, Texas, USA
| | - Suthat Liangpunsakul
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
- BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
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Loeb TA, Gunaratne MP, Iqbal S, Anderson M, McFall AM, Amrose P, Rodgers MA, Srikrishnan AK, Balagopal A, Lucas GM, Mehta SH, Thomas DL, Cloherty G, Thio CL, Solomon SS. Hepatitis B Virus in People who Inject Drugs and Men who Have Sex With Men With HIV in India: A Cross-sectional Study. Open Forum Infect Dis 2024; 11:ofae350. [PMID: 39022392 PMCID: PMC11252851 DOI: 10.1093/ofid/ofae350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 06/26/2024] [Indexed: 07/20/2024] Open
Abstract
Background People with HIV (PWH) who are coinfected with hepatitis B virus (HBV) have a higher risk of mortality compared with PWH alone. Populations such as people who inject drugs (PWID) and men who have sex with men (MSM) are particularly at high risk for HBV acquisition; yet, limited epidemiological data from these populations exist on HBV prevalence from low- and middle-income country settings (LMICs). Methods We characterized the prevalence and correlates of HBV serological markers in a sample of PWID and MSM with HIV recruited across 15 Indian cities using hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and hepatitis B surface antibody (anti-HBs). Testing of stored specimens for the presence of these markers was performed on the Abbott ARCHITECT i1000 as per the manufacturer's instructions. Correlates of ever being infected with HBV (reactive for anti-HBc and/or HBsAg) and chronic HBV (reactive for HBsAg) among those ever infected were assessed using univariable and multivariable multilevel logistic regression models accounting for site-level clustering. Results A total of 2198 (95%) of the 2314 participants recruited for the trial were screened for HBV markers. The median age among the PWID and MSM participants was 30 and 32 years, respectively. The prevalence of ever being infected with HBV was 75.6% vs 46.9% in PWID vs MSM, respectively (P < .01); prevalence of chronic infection was also higher in PWID vs MSM (14.1% vs 9.5%; P < .01). Correlates of ever being infected with HBV among PWID included unstable housing (adjusted odds ratio [aOR], 5.02) and sharing injection paraphernalia (aOR, 2.70), and among MSM, correlates included history of injection drug use (aOR, 4.87) and gender identity. The prevalence of isolated core (anti-HBc in the absence of anti-HBs) was 34.7% vs 29.4% in PWID vs MSM (P < .05). Vaccination serostatus was <10% in both populations. Conclusions In this large sample of PWID and MSM with HIV, we observed a high prevalence of serology consistent with HBV infection and low vaccination, highlighting the need for routine screening and catch-up vaccination. The high prevalence of isolated anti-HBc reactivity highlights the need to understand the risk of reactivation with this serological pattern.
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Affiliation(s)
- Talia A Loeb
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Mihili P Gunaratne
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Syed Iqbal
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | | | - Allison M McFall
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Pradeep Amrose
- YR Gaitonde Centre for AIDS Research and Education, Chennai, India
| | | | | | - Ashwin Balagopal
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Gregory M Lucas
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Shruti H Mehta
- Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - David L Thomas
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | | | - Chloe L Thio
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Sunil S Solomon
- Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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7
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Anderson M, Mangogola T, Phinius BB, Mpebe G, Aimakhu CO, Choga WT, Phakedi B, Bhebhe LN, Ditshwanelo D, Baruti K, Mpofu-Dobo L, Othusitse L, Ratsoma T, Gaolathe T, Makhema J, Shapiro R, Lockman S, Moyo S, Gaseitsiwe S. Hepatitis B Virus Prevalence among HIV-Uninfected People Living in Rural and Peri-Urban Areas in Botswana. Microorganisms 2024; 12:1207. [PMID: 38930589 PMCID: PMC11205512 DOI: 10.3390/microorganisms12061207] [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: 05/07/2024] [Revised: 06/10/2024] [Accepted: 06/12/2024] [Indexed: 06/28/2024] Open
Abstract
(1) Background: we determined the prevalence of the hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened for the hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n = 2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013-2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24-46) and 64% (1360/2135) were female. HBV prevalence was 4.0% (86/2135) [95% CI: 3.3-4.9]) and ranged between 0-9.2%. Older participants (>35 years) had increased odds of HBV positivity (OR: 1.94; 95% CI: [1.32-2.86]; p = 0.001). Thirteen samples were sequenced and seven (53.8%) were genotype A, three (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3-4.9) among people without HIV in rural and peri-urban communities in Botswana with varying rates in different communities. A comprehensive national HBV program is required in Botswana to guide HBV prevention, testing and management.
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Affiliation(s)
- Motswedi Anderson
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Africa Health Research Institute, Durban 4013, South Africa
- The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK
| | - Thabo Mangogola
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Pan-African University (Life and Earth Sciences Institute), University of Ibadan, Ibadan 200132, Nigeria;
| | - Bonolo B. Phinius
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Gorata Mpebe
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Biological Sciences, Faculty of Science, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Christopher O. Aimakhu
- Pan-African University (Life and Earth Sciences Institute), University of Ibadan, Ibadan 200132, Nigeria;
| | - Wonderful T. Choga
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- School of Allied Health Professions, Faculty of Health Sciences, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Basetsana Phakedi
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
| | - Lynnette N. Bhebhe
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
| | - Doreen Ditshwanelo
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
| | - Kabo Baruti
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Biological Sciences, Faculty of Science, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Linda Mpofu-Dobo
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Biological Sciences and Biotechnology, Faculty of Sciences, Botswana International University of Science and Technology, Private Bag 16, Palapye, Botswana
| | - Lebogang Othusitse
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
| | - Tsholofelo Ratsoma
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Biological Sciences, Faculty of Science, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Tendani Gaolathe
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Faculty of Medicine, University of Botswana, Private Bag UB 0022, Gaborone, Botswana
| | - Joseph Makhema
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Roger Shapiro
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Shahin Lockman
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, MA 02115, USA
| | - Sikhulile Moyo
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
- Division of Medical Virology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Stellenbosch, Private Bag X1, Matieland 7602, South Africa
- School of Health Systems and Public Health, University of Pretoria, Private Bag X20, Pretoria 0028, South Africa
| | - Simani Gaseitsiwe
- Botswana Harvard Health Partnership, Private Bag BO320, Gaborone, Botswana; (M.A.); (T.M.); (B.B.P.); (G.M.); (W.T.C.); (B.P.); (L.N.B.); (D.D.); (K.B.); (L.M.-D.); (L.O.); (T.R.); (T.G.); (J.M.); (R.S.); (S.L.); (S.M.)
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
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Ali MJ, Shah PA, Rehman KU, Kaur S, Holzmayer V, Cloherty GA, Kuhns MC, Lau DTY. Immune-Escape Mutations Are Prevalent among Patients with a Coexistence of HBsAg and Anti-HBs in a Tertiary Liver Center in the United States. Viruses 2024; 16:713. [PMID: 38793596 PMCID: PMC11125813 DOI: 10.3390/v16050713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/21/2024] [Accepted: 04/27/2024] [Indexed: 05/26/2024] Open
Abstract
The concurrent seropositivity of HBsAg and anti-HBs has been described among patients with chronic hepatitis B (CHB), but its prevalence is variable. HBV S-gene mutations can affect the antigenicity of HBsAg. Patients with mutations in the 'α' determinant region of the S gene can develop severe HBV reactivation under immunosuppression. In this study at a tertiary liver center in the United States, we evaluated the frequency and virological characteristics of the HBsAg mutations among CHB patients with the presence of both HBsAg and anti-HBs. In this cohort, 45 (2.1%) of 2178 patients were identified to have a coexistence of HBsAg and anti-HBs, and 24 had available sera for the genome analysis of the Pre-S1, Pre-S2, and S regions. The frequency of mutations in the S gene was significantly higher among those older than 50 years (mean 8.5 vs. 5.4 mutations per subject, p = 0.03). Twelve patients (50%) had mutations in the 'α' determinant region of the S gene. Mutations at amino acid position 126 were most common in eight subjects. Three had a mutation at position 133. Only one patient had a mutation at position 145-the classic vaccine-escape mutation. Despite the universal HBV vaccination program, the vaccine-escape mutant is rare in our cohort of predominantly Asian patients.
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Affiliation(s)
- Mukarram Jamat Ali
- Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (M.J.A.); (P.A.S.); (K.U.R.); (S.K.)
- Howard University Hospital, Howard University College of Medicine, Washington, DC 20060, USA
| | - Pir Ahmed Shah
- Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (M.J.A.); (P.A.S.); (K.U.R.); (S.K.)
| | - Khalil Ur Rehman
- Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (M.J.A.); (P.A.S.); (K.U.R.); (S.K.)
| | - Satinder Kaur
- Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (M.J.A.); (P.A.S.); (K.U.R.); (S.K.)
| | - Vera Holzmayer
- Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL 60064, USA; (V.H.); (G.A.C.); (M.C.K.)
| | - Gavin A. Cloherty
- Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL 60064, USA; (V.H.); (G.A.C.); (M.C.K.)
| | - Mary C. Kuhns
- Abbott Diagnostics Division, Abbott Laboratories, Abbott Park, IL 60064, USA; (V.H.); (G.A.C.); (M.C.K.)
| | - Daryl T. Y. Lau
- Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; (M.J.A.); (P.A.S.); (K.U.R.); (S.K.)
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9
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Bujandric N, Grujic J, Milanovic MK. An interesting case of isolated false-negative hepatitis B surface antigen in a blood donor. Vox Sang 2023. [PMID: 38157225 DOI: 10.1111/vox.13581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 12/06/2023] [Accepted: 12/06/2023] [Indexed: 01/03/2024]
Abstract
BACKGROUND AND OBJECTIVES An important requirement for a hepatitis B surface antigen (HBsAg) screening assay is reliable detection of HBsAg mutant forms, especially in blood donation. Here we investigate and describe the case of an isolated false-negative result of commercial serology HBsAg screening assay of a blood donor. MATERIALS AND METHODS The current donation was routinely tested for HBsAg and hepatitis B virus (HBV) DNA in the mini-pool mode nucleic acid testing (MP-NAT of six samples), and further evaluated by individual donation ID-NAT. Finally, it was quantified and sequenced. All previous donations were found to have negative HBsAg and HBV DNA, as also the subsequent sample taken 3 months after the marked donation. RESULTS The current donation of the 53-year-old unvaccinated female with 14 previous donations was initially HBsAg negative and HBV DNA (MP-NAT) positive. Further testing showed HBsAg positive using other HBV serological assays, antibodies to HBV core antigen immunoglobulin M positive and HBV DNA ID-NAT positive, and contained 200 IU/mL of HBV DNA. The implicated donation carried genotype D strains, subtype ayw2 (F83S, V96A, V190A, L193S, I195T, L213S, F220L). The mutations in three positions, namely amino acids T118A, P120T, and P127T, were proven subsequently. CONCLUSION This unique mutation combination near the target epitope of one of the immunoassay monoclonals is a possible cause of the reduced analytical sensitivity of the serology assay.
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Affiliation(s)
- Nevenka Bujandric
- Department of Transfusiology, Faculty of Medicine University in Novi Sad, Novi Sad, Serbia
- Department of Laboratory Diagnostics, Blood Transfusion Institute of Vojvodina, Novi Sad, Serbia
| | - Jasmina Grujic
- Department of Transfusiology, Faculty of Medicine University in Novi Sad, Novi Sad, Serbia
- Department of Laboratory Diagnostics, Blood Transfusion Institute of Vojvodina, Novi Sad, Serbia
| | - Mirjana Krga Milanovic
- Department of Laboratory Diagnostics, Blood Transfusion Institute of Vojvodina, Novi Sad, Serbia
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10
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Wen X, Irshad A, Jin H. The Battle for Survival: The Role of RNA Non-Canonical Tails in the Virus-Host Interaction. Metabolites 2023; 13:1009. [PMID: 37755289 PMCID: PMC10537345 DOI: 10.3390/metabo13091009] [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: 08/05/2023] [Revised: 09/09/2023] [Accepted: 09/12/2023] [Indexed: 09/28/2023] Open
Abstract
Terminal nucleotidyltransferases (TENTs) could generate a 'mixed tail' or 'U-rich tail' consisting of different nucleotides at the 3' end of RNA by non-templated nucleotide addition to protect or degrade cellular messenger RNA. Recently, there has been increasing evidence that the decoration of virus RNA terminus with a mixed tail or U-rich tail is a critical way to affect viral RNA stability in virus-infected cells. This paper first briefly introduces the cellular function of the TENT family and non-canonical tails, then comprehensively reviews their roles in virus invasion and antiviral immunity, as well as the significance of the TENT family in antiviral therapy. This review will contribute to understanding the role and mechanism of non-canonical RNA tailing in survival competition between the virus and host.
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Affiliation(s)
| | | | - Hua Jin
- Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, No. 5 South Zhongguancun Street, Beijing 100081, China; (X.W.); (A.I.)
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11
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Ahmadi MH, Sharifi Z, Ghasemi A, Abbasian S. Occult hepatitis B in Iranian blood donors, an overview of the challenges: A narrative review. Health Sci Rep 2023; 6:e1466. [PMID: 37529253 PMCID: PMC10388709 DOI: 10.1002/hsr2.1466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/07/2023] [Accepted: 07/18/2023] [Indexed: 08/03/2023] Open
Abstract
Background Occult hepatitis B infection (OBI) is a transfusion-transmitted infection. Although, screening the hepatitis B virus among blood donors can play an important role in increasing the health of blood products, OBI screening in blood transfusion centers is still a challenge. This review study aimed to appraise the challenges of OBI screening and its associated do's and don'ts in blood transfusion centers. Methods In this review study, a search was conducted on the electronic databases of PubMed, Web of Science, Scopus, Ovid, Irandoc, and Magiran from January 1996 to December 2020. Also, cross-sectional studies that determined the prevalence of OBI or anti-HBc were included in the study. In addition, studies with incomplete data on the prevalence of OBI were excluded. Results The prevalence of OBI varies among Iranian blood donors. The rates reported by blood transfusion centers of Mashhad, Ahvaz, and Tehran were 0%, and Isfahan, Shiraz, and Kerman were 0.9%, 0.08%, and 2.36%, respectively. In areas with high prevalence of hepatitis B virus, OBI screening only by anti-HBc test led to the exemption of blood donors from donating blood. Avoiding OBI screening also effected the risk of virus transmission to blood recipients. Plasma products had a higher risk (85%) of virus transmission. Conclusions Determining an appropriate screening strategy based on prevalence status, the cost-effectiveness of screening tests, and the policies of each blood transfusion center is essential.
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Affiliation(s)
- Mohammad Hossein Ahmadi
- Department of Laboratory Science, School of Paramedical and Rehabilitation SciencesMashhad University of Medical SciencesMashhadIran
| | - Zohreh Sharifi
- Blood Transfusion Research CenterHigh Institute for Research and Education in Transfusion MedicineTehranIran
| | - Ali Ghasemi
- Departemant of Biochemistry and HematologyFaculty of Medicine Semnan University of Medical ScienceSemnanIran
| | - Sadegh Abbasian
- Student Research CommitteeIlam University of Medical SciencesIlamIran
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12
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Ahmadi Ghezeldasht S, Soleimanpour S, Hedayati-Moghaddam MR, Farshchian M, Rezaee SA, Mosavat A. Rate of occult hepatitis B virus infection among individuals with tuberculosis in northeastern Iran: A molecular epidemiological study. J Virus Erad 2023; 9:100333. [PMID: 37408699 PMCID: PMC10319180 DOI: 10.1016/j.jve.2023.100333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 05/31/2023] [Accepted: 06/14/2023] [Indexed: 07/07/2023] Open
Abstract
One third of the world population has a history of exposure to the hepatitis B virus (HBV), and two billion people are infected with latent tuberculosis (TB). Occult hepatitis B infection (OBI) is defined as the presence of replicative-competent HBV DNA in the liver with detectable or undetectable HBV DNA in the serum of individuals testing negative for the HBV surface antigen (HBsAg). Screening with HBV DNA could identify OBI and significantly reduce carriers and complications of chronic hepatitis B (CHB). This study aims to assess HBV serological markers and OBI molecular diagnosis among people with TB in Mashhad, northeastern Iran. We have performed HBV serological markers (HBsAg, HBc antibodies (Ab) and HBs Ab) in 175 participants. Fourteen HBsAg+ sera were excluded for further analysis. The presence of HBV DNA (C, S, and X gene regions) was assessed by the qualitative real-time PCR (qPCR) method. Frequencies of HBsAg, HBc, and HBs Ab were 8% (14/175), 36.6% (64/175), and 49.1% (86/175), respectively. Among these 42.9% (69/161) were negative for all HBV serological markers. The S, C, and X gene regions were positive in 10.3% (16/156), 15.4% (24/156), and 22.4% (35/156) of participants, respectively. The total OBI frequency was estimated at 33.3% (52/156) when based on detecting one HBV genomic region. Twenty-two and 30 participants had a seronegative and seropositive OBI, respectively. Thorough screening of high-risk groups with reliable and sensitive molecular methods could lead to OBI identification and decrease CHB long-term complications. Mass immunization remains critical in preventing, reducing, and potentially eliminating HBV complications.
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Affiliation(s)
- Sanaz Ahmadi Ghezeldasht
- Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran
| | - Saman Soleimanpour
- Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Reza Hedayati-Moghaddam
- Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran
| | - Moein Farshchian
- Division of Oncology, Laboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of Modena and Reggio Emilia, Modena, Italy
| | - Seyed Abdolrahim Rezaee
- Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arman Mosavat
- Blood Borne Infections Research Center, Academic Center for Education, Culture, and Research (ACECR), Razavi Khorasan, Mashhad, Iran
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13
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Steve RJ, Prakash A, Ponnuvel S, Dickson CJ, Nandan K, Singh B, Sam GA, Goel A, Zachariah UG, Eapen CE, Kannangai R, Abraham P, Fletcher GJ. Versatile performance edges of HBsAg Next assay in diagnosis and therapeutic monitoring of HBV infection. J Clin Virol 2023; 160:105378. [PMID: 36641983 DOI: 10.1016/j.jcv.2023.105378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 12/27/2022] [Accepted: 01/05/2023] [Indexed: 01/12/2023]
Abstract
BACKGROUND HBsAg Next assay (HBsAgNx) claims improved detection of HBsAg. The aim was to investigate its performance in ascertaining HBsAg loss, ability to detect HBsAg in various phases of HBV infection, specificity and its amenability to in-house neutralization. METHODS Analytical sensitivity was investigated using NIBSC standard (3rd WHO-IS). For clinical performance, out of 91,962 samples tested for HBsAg (Qual-II), 512 samples consisting of 170 cases with evidence of HBsAg loss during treatment (n = 116) and without treatment (n = 54), acute-hepatitis B (n = 90) and acute exacerbation of chronic-hepatitis B (n = 41), acute-hepatitis A (n = 24) and acute-hepatitis E (n = 9) positive, HIV-1 positive (n = 20), non-HBV, HAV and HEV related acute-hepatitis (n = 81) and HBsAg prozone (n = 14) as well as in-house neutralization (n = 63) were included. RESULTS The calculated limit of detection (LOD) was 0.004 IU/mL. Of the 170 patients with apparent HBsAg loss, 18/116 (15.5%) among treated and 15/54 (27.7%) with spontaneous clearance were positive in HBsAgNx (p < 0.0001). Additionally, it detected HBsAg in 12/95 (12.6%) and 6/34 (17.6%) patients who were HBV DNA negative in treatment experienced and spontaneous clearance groups respectively (p < 0.001). The specificity of HBsAgNx was comparable to HBsAg Qual-II. The signal-intensity of HBsAgNx was significantly higher than HBsAg Qual-II across various phases of HBV infection and prozone samples. CONCLUSION HBsAgNx significantly enhanced the accuracy of HBsAg detection without compromising the specificity in ascertaining HBsAg loss. The performance was superior in various phases of HBV infection including samples that exhibited prozone effect. Furthermore, it is amenable to cost-effective in-house neutralization to confirm low HBsAg levels.
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Affiliation(s)
- Runal John Steve
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Arul Prakash
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Suresh Ponnuvel
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | | | - Karthick Nandan
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Bakthalal Singh
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Gift Ajay Sam
- Department of Transfusion Medicine and Immuno-haematology, Christian Medical College, Vellore, India
| | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, India
| | | | | | - Rajesh Kannangai
- Department of Clinical Virology, Christian Medical College, Vellore, India
| | - Priya Abraham
- Department of Clinical Virology, Christian Medical College, Vellore, India
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14
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Sun H, Chang L, Yan Y, Ji H, Jiang X, Song S, Xiao Y, Lu Z, Wang L. Naturally occurring pre-S mutations promote occult HBV infection by affecting pre-S2/S promoter activity. Antiviral Res 2022; 208:105448. [DOI: 10.1016/j.antiviral.2022.105448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 10/08/2022] [Accepted: 10/12/2022] [Indexed: 11/15/2022]
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15
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Campos-Valdez M, Feustel S, Monroy-Ramírez HC, Barrientos-Salcedo C, Ayón-Pérez MF, Ramos-Márquez ME, Fernández-Galindo DA, Silva-Gómez JA, Santos A, Armendáriz-Borunda J, Sánchez-Orozco LV. Influence of C107R mutation from hepatitis B virus genotype H on in vitro hepatitis B surface antigen detection and IFN-β-1a treatment. Future Virol 2022. [DOI: 10.2217/fvl-2021-0347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Aim: Assess the in vitro effect of hepatitis B virus (HBV) genotype H (HBV/H) with the small surface HBV protein (HBs) C107R mutation on hepatitis B surface antigen (HBsAg) detection, TGFB1, CAT and IFNB1A expression, and the response to IFN-β-1a treatment. Methods: HBV/H wild-type and HBs C107R variant replicons were constructed and transfected into hepatic stellate cells and/or Huh7 that were later treated with IFN-β-1a. HBsAg, HBV-DNA, pgRNA, TGFB1, CAT and IFNB1A expression was analyzed. 3D HBs structure from wild-type and C107R were foreseen by AlphaFold protein predictor, and IFN-β-1a antiviral effect was evaluated. Results: C107R mutation did not impact viral replication, but HBsAg serologic detection was affected. Wild-type and C107R similarly modified gene expression and responded to IFN-β-1a. Conclusion: C107R disrupts the Cys107/Cys138 disulfide bond and impairs HBsAg detection. Independently of the mutation, there were changes in TGFB1, CAT and IFNB1A expression, and a medium response to IFN-β-1a treatment compared with genotype A and C.
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Affiliation(s)
- Marina Campos-Valdez
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - Sina Feustel
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - Hugo Christian Monroy-Ramírez
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - Carolina Barrientos-Salcedo
- Laboratorio de Química Médica y Quimiogenómica, Facultad de Bioanálisis, Universidad Veracruzana, Veracruz, México
| | | | - Martha Eloísa Ramos-Márquez
- Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - David A Fernández-Galindo
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - Jorge Antonio Silva-Gómez
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
| | - Arturo Santos
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Campus Guadalajara, Zapopan, Jalisco, 45201, México
| | - Juan Armendáriz-Borunda
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Campus Guadalajara, Zapopan, Jalisco, 45201, México
| | - Laura Verónica Sánchez-Orozco
- Instituto de Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
- Instituto de Enfermedades Crónico Degenerativas, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, 44340, México
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Yu Y, Zhang Y, Dai Y, Sun Q, Jiang C, Xu X, Mei C, Cheng J. Analysis of S gene characteristic sequences and changes in properties of protein expression in HBV ASCs with low-level HBsAg. Front Med (Lausanne) 2022; 9:948842. [PMID: 36186824 PMCID: PMC9516100 DOI: 10.3389/fmed.2022.948842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 08/22/2022] [Indexed: 11/26/2022] Open
Abstract
Objective We detected the serum HBsAg immune complex (HBsAg-CIC) and sequenced the HBV S gene in these patients to reveal the association between sustained low-level expression of HBsAg and mutated S gene sequence characteristics, protein function changes, and HBsAg immune complex formation. Methods A total of 204 samples were collected and divided into high-level (n = 60, HBsAg level >10 IU/ml) and low-level (n = 144, HBsAg level ≤ 10 IU/ml) HBsAg groups. The clinical and epidemiological data of the two groups were statistically compared. According to different serological patterns and genotypes, the HBsAg-CIC results of the high-level and low-level HBsAg groups were divided into different subgroups, and then the HBsAg-CIC positive rates among different subgroups were compared. We sequenced the S gene of HBV from the two groups and identified the relevant mutations in the MHR of the S gene. In addition, we compared the changes in HBsAg protein properties and functions after hot spot mutation in the MHR of the S gene. Results Comparing the positive rates of HBsAg-CIC under different serological patterns and genotypes in the two groups, the HBsAg-CIC positive rate was higher in the low-level HBsAg group. Moreover, there was weak correlation between HBsAg-CIC and HBsAg or HBV DNA in both groups (r = 0.32, 0.27, 0.41, 0.48; P < 0.05). Sequencing of S gene in the two groups, showed that the hot-spot mutations were T126A, M133L/T/S, and F134L/T/I in MHR of S gene of genotype B, and hot-spot mutations were Q101R and I126S/T in MHR of S gene of genotype C. Additionally, the positive rate of MHR mutation in the S gene from HBsAg-CIC positive patients was higher in the low-level HBsAg group. Conclusion The host immune process of clearing HBV seems to have multiple site mutations in MHR, which changes the physicochemical properties and functions of HBsAg and intensifies the formation of HBsAg-CIC, thus avoiding the effective recognition of HBsAg by the host and resulting in immune tolerance between the host and HBV, which may be one of the formation mechanisms of sustained low-level expression of HBsAg in the serum of HBV-infected persons.
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Affiliation(s)
- Yu Yu
- School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
- Department of Clinical Research, The 903rd Hospital of PLA, Hangzhou, China
| | - Yingqiang Zhang
- Department of Clinical Research, The 903rd Hospital of PLA, Hangzhou, China
| | - Yuzhu Dai
- School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
- Department of Clinical Research, The 903rd Hospital of PLA, Hangzhou, China
| | - Qingyang Sun
- Department of Clinical Research, The 903rd Hospital of PLA, Hangzhou, China
| | - Chun Jiang
- Department of Clinical Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China
| | - Xujian Xu
- Department of Biotechnology, The University of Tokyo, Tokyo, Japan
| | - Chuanzhong Mei
- School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
- Chuanzhong Mei
| | - Jun Cheng
- School of Laboratory Medicine, Bengbu Medical College, Bengbu, China
- Department of Clinical Research, The 903rd Hospital of PLA, Hangzhou, China
- Faculty of Graduate Studies, Jiangsu University, Zhenjiang, China
- *Correspondence: Jun Cheng
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Ostankova YV, Serikova EN, Semenov AV, Totolian AA. Method for hepatitis B virus DNA detecting in biological material at low viral load based on nested PCR with detection on three viral targets in real-time mode. Klin Lab Diagn 2022; 67:530-537. [PMID: 36099463 DOI: 10.51620/0869-2084-2022-67-9-530-537] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
A method has been developed for HBV DNA finding in biological material at low viral load based on nested PCR with real-time detection of three viral targets. When developing the method, blood plasma samples were used from 128 CHB patients living in the regions of the Russian Federation and countries of Central Asia and 173 hemodialysis center patients living in the North-West Federal District. Analytical sensitivity was tested using the stepwise dilution method. HBV was detected by nested PCR. According to the method developed by us, at the first stage, the HBV DNA is amplified using at the first stage oligonucleotides complementary to the greatest similarity regions of the various HBV isolates genomes flanking the entire virus genome. At the second stage, when using the amplification product of the first stage as a template, PCR was performed using three pairs of oligonucleotides and the corresponding oligonucleotide fluorescently labeled probes to three virus genome regions (Core gene, S gene and X gene), as well as one pair of primers and the corresponding probe complementary to a human HPRT gene region. The method sensitivity for DNA extraction from plasma with a 100 μl volume was 10 IU/ml. Obtaining a threshold Ct cycle for only one fluorophore may indicate the presence of HBV DNA in the sample at a load of less than 10 IU/ml, HBV detection in this case is possible with a repeated PCR study of the corresponding sample with HBV DNA extraction from an increased plasma volume (200-1000 μl). The developed method makes it possible to identify the disease in various HBV subgenotypes and can be used to diagnose CHB in the population and risk groups, including those with the HBsAg-negative form of the disease.
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Gherlan GS. Occult hepatitis B - the result of the host immune response interaction with different genomic expressions of the virus. World J Clin Cases 2022; 10:5518-5530. [PMID: 35979101 PMCID: PMC9258381 DOI: 10.12998/wjcc.v10.i17.5518] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 01/30/2022] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
With over 40 years of history, occult hepatitis B infection (OBI) continues to remain an important and challenging public health problem. Defined as the presence of replication-competent hepatitis B virus (HBV) DNA (i.e., episomal HBV covalently closed circular DNA) in the liver and/or HBV DNA in the blood of people who test negative for hepatitis B surface antigen (HBsAg) in currently available assays, OBI is currently diagnosed using polymerase chain reaction (PCR) and real-time PCR assays. However, all efforts should be made to exclude a false negative HBsAg in order to completely follow the definition of OBI. In recent years, significant advances have been made in understanding the HBV lifecycle and the molecular mechanisms that lead to the persistence of the virus in the occult form. These factors are mainly related to the host immune system and, to a smaller proportion, to the virus. Both innate and adaptive immune responses are important in HBV infection management, and epigenetic changes driven by host mechanisms (acetylation, methylation, and microRNA implication) are added to such actions. Although greater genetic variability in the S gene of HBV isolated from OBIs was found compared with overt infection, the mechanisms of OBI are not mainly viral mutations.
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Affiliation(s)
- George Sebastian Gherlan
- Department of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, Bucharest 030303, Romania
- Department of Infectious Diseases, “Dr. Victor Babes” Hospital of Infectious and Tropical Diseases, Bucharest 030303, Romania
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Yuan C, Peng J, Xia R, He J, Qiu T, Yao Y. Reactivation of Occult Hepatitis B Virus Infection During Long-Term Entecavir Antiviral Therapy. Front Microbiol 2022; 13:865124. [PMID: 35359734 PMCID: PMC8960739 DOI: 10.3389/fmicb.2022.865124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 02/14/2022] [Indexed: 12/15/2022] Open
Abstract
Up to now, it has not been clear whether occult hepatitis B virus (HBV) infection (OBI) can be treated with antiviral therapy whether OBI can develop drug resistance gene mutation or not. We report a middle-aged female patient with OBI who showed HBV reactivation (HBVr) during more than 3 years of intermittent entecavir (ETV) antiviral therapy: seropositive HBV surface antigen (HBsAg), increased e antigen (HBeAg), and repeatedly elevated serum HBV DNA. Genotype analysis showed that the patient was infected with HBV type B. Genetic sequencing of HBV showed the mutants of S143T, D144G, and G145R in the S gene region, and the mutant of site 1896 in the pre-Core region coexisted with the wild type (G1896A/G). No mutation was found in other HBV gene segments. Drug resistance gene analysis found RtL229W mutant, resistant to lamivudine but sensitive to ETV and other nucleoside analogs. This case of OBI provides us with the following clinical experiences: Firstly, it is necessary to detect HBV genotype, mutation, and drug-resistant genes at the initial diagnosis, which can be helpful for reasonable treatment. Secondly, identifying the risk factors and mechanisms associated with HBVr could help quantify the risk of HBVr and manage the clinical consequences. Thirdly, the OBI patients with hepatitis B e antigen-positive, HBV DNA > 1 × 103 IU/ml should be recommended regular and continuous antiviral therapy as soon as possible to prevent the occurrence of hepatocirrhosis and hepatocellular carcinoma (HCC).
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