1
|
Jhelum H, Kaufer B, Denner J. Application of Methods Detecting Xenotransplantation-Relevant Viruses for Screening German Slaughterhouse Pigs. Viruses 2024; 16:1119. [PMID: 39066281 PMCID: PMC11281539 DOI: 10.3390/v16071119] [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] [Academic Contribution Register] [Received: 06/21/2024] [Revised: 07/09/2024] [Accepted: 07/10/2024] [Indexed: 07/28/2024] Open
Abstract
Detection methods have been developed to prevent transmission of zoonotic or xenozoonotic porcine viruses after transplantation of pig organs or cells to the recipient (xenotransplantation). Eleven xenotransplantation-relevant viruses, including porcine cytomegalovirus, porcine roseolovirus (PCMV/PRV), porcine lymphotropic herpesviruses -1, -2, -3 (PLHV-1, 2, 3), porcine parvovirus (PPV), porcine circovirus 2, 3, 4 (PCV2, 3, 4), hepatitis E virus genotype 3 (HEV3), porcine endogenous retrovirus-C (PERV-C), and recombinant PERV-A/C have been selected. In the past, several pig breeds, minipigs, and genetically modified pigs generated for xenotransplantation had been analyzed using these methods. Here, spleen, liver, and blood samples from 10 German slaughterhouse pigs were screened using both PCR-based and immunological assays. Five viruses: PCMV/PRV, PLHV-1, PLHV-3, and PERV-C, were found in all animals, and PCV3 in one animal. Some animals were latently infected with PCMV/PRV, as only virus-specific antibodies were detected. Others were also PCR positive in the spleen and/or liver, indicative of an ongoing infection. These results provide important information on the viruses that infect German slaughterhouse pigs, and together with the results of previous studies, they reveal that the methods and test strategies efficiently work under field conditions.
Collapse
Affiliation(s)
| | | | - Joachim Denner
- Institute of Virology, Free University Berlin, 14163 Berlin, Germany; (H.J.); (B.K.)
| |
Collapse
|
2
|
Yadav KK, Boley PA, Lee CM, Khatiwada S, Jung K, Laocharoensuk T, Hofstetter J, Wood R, Hanson J, Kenney SP. Rat hepatitis E virus cross-species infection and transmission in pigs. PNAS NEXUS 2024; 3:pgae259. [PMID: 39035038 PMCID: PMC11259135 DOI: 10.1093/pnasnexus/pgae259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Academic Contribution Register] [Received: 08/28/2023] [Accepted: 06/14/2024] [Indexed: 07/23/2024]
Abstract
Strains of Rocahepevirus ratti, an emerging hepatitis E virus (HEV), have recently been found to be infectious to humans. Rats are a primary reservoir of the virus; thus, it is referred to as "rat HEV". Rats are often found on swine farms in close contact with pigs. Our goal was to determine whether swine may serve as a transmission host for zoonotic rat HEV by characterizing an infectious cDNA clone of a zoonotic rat HEV, strain LCK-3110, in vitro and in vivo. RNA transcripts of LCK-3110 were constructed and assessed for their replicative capacity in cell culture and in gnotobiotic pigs. Fecal suspension from rat HEV-positive gnotobiotic pigs was inoculated into conventional pigs co-housed with naïve pigs. Our results demonstrated that capped RNA transcripts of LCK-3110 rat HEV replicated in vitro and successfully infected conventional pigs that transmit the virus to co-housed animals. The infectious clone of rat HEV may afford an opportunity to study the genetic mechanisms of rat HEV cross-species infection and tissue tropism.
Collapse
Affiliation(s)
- Kush Kumar Yadav
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
| | - Patricia A Boley
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
| | - Carolyn M Lee
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
| | - Saroj Khatiwada
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
| | - Kwonil Jung
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
| | - Thamonpan Laocharoensuk
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
| | - Jake Hofstetter
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
| | - Ronna Wood
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
| | - Juliette Hanson
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
| | - Scott P Kenney
- Department of Animal Sciences, Center for Food Animal Health, The Ohio State University, 1680 Madison Ave, Wooster, OH 44691, USA
- Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, 1900 Coffey Road, Columbus, OH 43210, USA
| |
Collapse
|
3
|
Zhang H, Li X, Wang C, Shi T, Geng Y, Zhao C. Detection of Hepatitis E Virus in Rabbits and Rabbit Meat from Slaughterhouses in Hebei Province of China. Vector Borne Zoonotic Dis 2023; 23:588-594. [PMID: 37699252 DOI: 10.1089/vbz.2023.0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 09/14/2023] Open
Abstract
Background: Hepatitis E virus (HEV) is a zoonotic pathogen. HEV has been found to be widely prevalent in rabbits. Its isolates are classified into HEV-3, rabbit subgenotype (HEV-3ra). The routes of human infection with HEV-3ra remain unclear; however, foodborne transmission is possible when asymptomatically infected animals enter the food chain. The prevalence of HEV infection in slaughtered rabbits and the presence of HEV in rabbit meat were evaluated in this study. Materials and Methods: In three slaughterhouses in Hebei province, China, samples of rabbit blood were collected during the slaughter process, and muscle, liver, and cavity juice were collected from the rabbit carcasses. Anti-HEV antibody in serum samples was detected using enzyme-linked immunosorbent assay. HEV RNA was tested in all samples by reverse transcription nested PCR (RT-nested PCR). The final amplicons of RT-nested PCR were sequenced and phylogenetically analyzed. Results: Of the 459 serum samples, 50 [10.9%, 95% confidence interval (CI): 8.1-13.7] were positive for anti-HEV antibody, and 17 (3.7%, 95% CI: 2.0-5.4) were positive for HEV RNA. HEV RNA was detected in 7 of 60 liver samples (11.7%, 95% CI: 3.3-20) and 2 cavity juice samples from semi-eviscerated carcasses, but was not detected in any muscle sample from either the eviscerated or semi-eviscerated carcasses. All the detected HEV strains belonged to HEV-3ra and related most closely with the rabbit HEV sequence previously reported in China. Conclusion: A portion of rabbits were in the viremia period of HEV infection at the slaughter age, resulting in the possibility of HEV carriage by rabbit carcass, particularly semi-eviscerated carcass containing liver. These findings suggest a potential risk of HEV transmission from raw rabbit products entering the food chain, whereas the presence of HEV appeared to be lower in the eviscerated carcass than in the semi-eviscerated carcass.
Collapse
Affiliation(s)
- Hongxin Zhang
- Key Laboratory of Public Health Safety of Hebei Province, Department of Preventive Medicine, School of Public Health, Hebei University, Baoding, China
| | - Xueli Li
- Key Laboratory of Public Health Safety of Hebei Province, Department of Preventive Medicine, School of Public Health, Hebei University, Baoding, China
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| | - Chunyan Wang
- Division of Epidemiology, Baoding Centre for Disease Control and Prevention, Baoding, China
| | - Tengfei Shi
- Key Laboratory of Public Health Safety of Hebei Province, Department of Preventive Medicine, School of Public Health, Hebei University, Baoding, China
| | - Yansheng Geng
- Key Laboratory of Public Health Safety of Hebei Province, Department of Preventive Medicine, School of Public Health, Hebei University, Baoding, China
| | - Chenyan Zhao
- Division of HIV/AIDS and Sex-Transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China
| |
Collapse
|
4
|
Turlewicz-Podbielska H, Augustyniak A, Wojciechowski J, Pomorska-Mól M. Hepatitis E Virus in Livestock-Update on Its Epidemiology and Risk of Infection to Humans. Animals (Basel) 2023; 13:3239. [PMID: 37893962 PMCID: PMC10603682 DOI: 10.3390/ani13203239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 09/22/2023] [Revised: 10/09/2023] [Accepted: 10/16/2023] [Indexed: 10/29/2023] Open
Abstract
Hepatitis E virus (HEV) is a public health problem worldwide and an important food pathogen known for its zoonotic potential. Increasing numbers of infection cases with human HEV are caused by the zoonotic transmission of genotypes 3 and 4, mainly by consuming contaminated, undercooked or raw porcine meat. Pigs are the main reservoir of HEV. However, it should be noted that other animal species, such as cattle, sheep, goats, and rabbits, may also be a source of infection for humans. Due to the detection of HEV RNA in the milk and tissues of cattle, the consumption of infected uncooked milk and meat or offal from these species also poses a potential risk of zoonotic HEV infections. Poultry infected by avian HEV may also develop symptomatic disease, although avian HEV is not considered a zoonotic pathogen. HEV infection has a worldwide distribution with different prevalence rates depending on the affected animal species, sampling region, or breeding system.
Collapse
Affiliation(s)
- Hanna Turlewicz-Podbielska
- Department of Preclinical Sciences and Infectious Diseases, Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland; (H.T.-P.); (A.A.)
| | - Agata Augustyniak
- Department of Preclinical Sciences and Infectious Diseases, Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland; (H.T.-P.); (A.A.)
| | | | - Małgorzata Pomorska-Mól
- Department of Preclinical Sciences and Infectious Diseases, Poznan University of Life Sciences, Wolynska 35, 60-637 Poznan, Poland; (H.T.-P.); (A.A.)
| |
Collapse
|
5
|
Arce LP, Pavan MF, Bok M, Gutiérrez SE, Estein SM, Santos AT, Condorí WE, Uhart MM, Parreño V, Vizoso-Pinto MG, Ibañez LI. A multispecies competitive nanobody-based ELISA for the detection of antibodies against hepatitis E virus. Sci Rep 2023; 13:15448. [PMID: 37723180 PMCID: PMC10507121 DOI: 10.1038/s41598-023-41955-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 04/18/2023] [Accepted: 09/04/2023] [Indexed: 09/20/2023] Open
Abstract
The hepatitis E virus (HEV) is an emergent zoonotic virus causing viral hepatitis worldwide. Clinically, hepatitis E is not easily distinguished from other types of acute viral hepatitis. There is a need for HEV diagnostic assays to detect and prevent interspecies transmission among susceptible populations. Nanobodies (Nbs) are expressed recombinantly in different systems, produced with high yields, and have superior physicochemical properties compared with conventional antibodies (Ab). Several Nbs against ORF2, the capsid protein and main antigen, were selected and produced in E. coli. Nb39 and Nb74 specifically recognized HEV ORF2 (genotypes 3 and 4). A competitive ELISA (cELISA) was developed and validated using a reference panel of human (n = 86) and swine sera (n = 116) tested in comparison with a commercial kit. The optimal cutoff values determined by ROC analysis were 69.16% (human) and 58.76% (swine); the sensitivity and specificity were high: 97.4% (95% CI 86.5-99.5%) and 95.8% (95% CI 86.0-98.8%) for human vs. 100% (95% CI 93.5-100%) and 98.3% (95% CI 91.0-99.7%) for swine. Further, the cELISA detected total anti-HEV antibodies in wild boar, deer, and mice. To our knowledge, this is the first report of production of Nbs against HEV-3 ORF2 for diagnostic purposes.
Collapse
Affiliation(s)
- Lorena Paola Arce
- Infection Biology Laboratory, Faculty of Medicine and Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, T4000ILI, Tucumán, Argentina
- Laboratorio de Ingeniería de Anticuerpos, Instituto de Química, Física de los Materiales, Medio ambiente y Energía (INQUIMAE-CONICET), C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina
| | - María Florencia Pavan
- Laboratorio de Ingeniería de Anticuerpos, Instituto de Química, Física de los Materiales, Medio ambiente y Energía (INQUIMAE-CONICET), C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina
| | - Marina Bok
- IncuINTA, Instituto de Virología, Instituto Nacional de Tecnología Agropecuaria (INTA), 1686, Husrlingham, Argentina
| | - Silvina Elena Gutiérrez
- Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Núcleo SAMP, Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), B7000GHG, Tandil, Buenos Aires, Argentina
| | - Silvia Marcela Estein
- Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Núcleo SAMP, Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), B7000GHG, Tandil, Buenos Aires, Argentina
| | - Agostina Tammone Santos
- Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Núcleo SAMP, Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), B7000GHG, Tandil, Buenos Aires, Argentina
| | - Walter Ezequiel Condorí
- Universidad Nacional del Centro de la Provincia de Buenos Aires, Facultad de Ciencias Veterinarias, Núcleo SAMP, Centro de Investigación Veterinaria de Tandil (UNCPBA-CICPBA-CONICET), B7000GHG, Tandil, Buenos Aires, Argentina
| | - Marcela María Uhart
- One Health Institute, School of Veterinary Medicine, University of California Davis, Davis, CA, 95616, USA
| | - Viviana Parreño
- IncuINTA, Instituto de Virología, Instituto Nacional de Tecnología Agropecuaria (INTA), 1686, Husrlingham, Argentina
| | - María Guadalupe Vizoso-Pinto
- Infection Biology Laboratory, Faculty of Medicine and Instituto Superior de Investigaciones Biológicas (INSIBIO), CONICET-UNT, T4000ILI, Tucumán, Argentina.
| | - Lorena Itatí Ibañez
- Laboratorio de Ingeniería de Anticuerpos, Instituto de Química, Física de los Materiales, Medio ambiente y Energía (INQUIMAE-CONICET), C1428EGA, Ciudad Autónoma de Buenos Aires, Argentina.
| |
Collapse
|
6
|
Monini M, Di Bartolo I, De Sabato L, Ianiro G, Agostinelli F, Ostanello F. Hepatitis E Virus (HEV) in Heavy Pigs in Slaughterhouses of Northern Italy: Investigation of Seroprevalence, Viraemia, and Faecal Shedding. Animals (Basel) 2023; 13:2942. [PMID: 37760342 PMCID: PMC10525452 DOI: 10.3390/ani13182942] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 08/08/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Hepatitis E virus (HEV) is considered an emerging threat in Europe, owing to the increased number of human cases and the widespread presence of the virus in pigs at farms. Most cases in industrialized countries are caused by the zoonotic HEV-3 genotype. The main transmission route of HEV-3 in Europe is foodborne, through consumption of raw or undercooked liver pork and wild boar meat. Pigs become susceptible to HEV infection after the loss of maternal immunity, and the majority of adult pigs test positive for IgG anti-HEV antibodies. Nonetheless, HEV-infected pigs in terms of liver, faeces, and rarely blood are identified at slaughterhouses. The present study aimed to investigate the prevalence of HEV-positive batches of Italian heavy pigs at slaughterhouses, assessing the presence of animals still shedding HEV upon their arrival at the slaughterhouse by sampling faeces collected from the floor of the trucks used for their transport. The occurrence of viraemic animals and the seroprevalence of anti-HEV antibodies were also assessed. The results obtained indicated the presence of anti-HEV IgM (1.9%), and a high seroprevalence of anti-HEV total antibodies (IgG, IgM, IgA; 89.2%, n = 260). HEV RNA was not detected in either plasma or faecal samples. Nevertheless, seropositive animals were identified in all eight batches investigated, confirming the widespread exposure of pigs to HEV at both individual and farm levels. Future studies are needed to assess the factors associated with the risk of HEV presence on farms, with the aim to prevent virus introduction and spread within farms, thereby eliminating the risk at slaughterhouse.
Collapse
Affiliation(s)
- Marina Monini
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (M.M.); (L.D.S.); (G.I.); (F.A.)
| | - Ilaria Di Bartolo
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (M.M.); (L.D.S.); (G.I.); (F.A.)
| | - Luca De Sabato
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (M.M.); (L.D.S.); (G.I.); (F.A.)
| | - Giovanni Ianiro
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (M.M.); (L.D.S.); (G.I.); (F.A.)
| | - Francesca Agostinelli
- Department of Food Safety, Nutrition and Veterinary Public Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy; (M.M.); (L.D.S.); (G.I.); (F.A.)
| | - Fabio Ostanello
- Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, Ozzano dell’Emilia, 40064 Bologna, Italy;
| |
Collapse
|
7
|
Koutsoumanis K, Allende A, Alvarez Ordoñez A, Bolton D, Bover‐Cid S, Chemaly M, Herman L, Hilbert F, Lindqvist R, Nauta M, Nonno R, Peixe L, Skandamis P, Suffredini E, Fernandez Escamez P, Gonzales‐Barron U, Roberts H, Ru G, Simmons M, Cruz RB, Lourenço Martins J, Messens W, Ortiz‐Pelaez A, Simon AC, De Cesare A. Assessment on the efficacy of methods 2 to 5 and method 7 set out in Commission Regulation (EU) No 142/2011 to inactivate relevant pathogens when producing processed animal protein of porcine origin intended to feed poultry and aquaculture animals. EFSA J 2023; 21:e08093. [PMID: 37416785 PMCID: PMC10320699 DOI: 10.2903/j.efsa.2023.8093] [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] [Academic Contribution Register] [Indexed: 07/08/2023] Open
Abstract
An assessment was conducted on the level of inactivation of relevant pathogens that could be present in processed animal protein of porcine origin intended to feed poultry and aquaculture animals when methods 2 to 5 and method 7, as detailed in Regulation (EU) No 142/2011, are applied. Five approved scenarios were selected for method 7. Salmonella Senftenberg, Enterococcus faecalis, spores of Clostridium perfringens and parvoviruses were shortlisted as target indicators. Inactivation parameters for these indicators were extracted from extensive literature search and a recent EFSA scientific opinion. An adapted Bigelow model was fitted to retrieved data to estimate the probability that methods 2 to 5, in coincidental and consecutive modes, and the five scenarios of method 7 are able to achieve a 5 log10 and a 3 log10 reduction of bacterial indicators and parvoviruses, respectively. Spores of C. perfringens were the indicator with the lowest probability of achieving the target reduction by methods 2 to 5, in coincidental and consecutive mode, and by the five considered scenarios of method 7. An expert knowledge elicitation was conducted to estimate the certainty of achieving a 5 log10 reduction of spores of C. perfringens considering the results of the model and additional evidence. A 5 log10 reduction of C. perfringens spores was judged: 99-100% certain for methods 2 and 3 in coincidental mode; 98-100% certain for method 7 scenario 3; 80-99% certain for method 5 in coincidental mode; 66-100% certain for method 4 in coincidental mode and for method 7 scenarios 4 and 5; 25-75% certain for method 7 scenario 2; and 0-5% certain for method 7 scenario 1. Higher certainty is expected for methods 2 to 5 in consecutive mode compared to coincidental mode.
Collapse
|
8
|
Mao H, Li J, Liao G, Gao M, Yang G, Bao J. The prevention strategies of swine viruses related to xenotransplantation. Virol J 2023; 20:121. [PMID: 37312151 PMCID: PMC10262131 DOI: 10.1186/s12985-023-02090-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/27/2023] [Accepted: 06/02/2023] [Indexed: 06/15/2023] Open
Abstract
Xenotransplantation is considered a solution for the shortage of organs, and pigs play an indispensable role as donors in xenotransplantation. The biosecurity of pigs, especially the zoonotic viruses carried by pigs, has attracted attention. This review introduces several viruses, including porcine endogenous retroviruses that are integrated into the pig genome in a DNA form, herpesviruses that have been proven to clearly affect recipient survival time in previous xenotransplant surgeries, the zoonotic hepatitis E virus, and the widely distributed porcine circoviruses. The detail virus information, such as structure, caused diseases, transmission pathways, and epidemiology was introduced in the current review. Diagnostic and control measures for these viruses, including detection sites and methods, vaccines, RNA interference, antiviral pigs, farm biosecurity, and drugs, are discussed. The challenges faced, including those posed by other viruses and newly emerged viruses, and the challenges brought by the modes of transmission of the viruses are also summarized.
Collapse
Affiliation(s)
- Hongzhen Mao
- Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China
- Center of Infectious Diseases & Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jinyang Li
- Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Guangneng Liao
- Experimental Animal Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Mengyu Gao
- Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Guang Yang
- Experimental Animal Center, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Ji Bao
- Institute of Clinical Pathology, Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, 610041, China.
| |
Collapse
|
9
|
Hansen S, Fischer K, Krabben L, Rinke Carrapeiro A, Klinger B, Schnieke A, Kaufer B, Denner J. Detection of porcine cytomegalovirus, a roseolovirus, in pig ovaries and follicular fluid: implications for somatic cells nuclear transfer, cloning and xenotransplantation. Virol J 2023; 20:15. [PMID: 36707837 PMCID: PMC9881377 DOI: 10.1186/s12985-023-01975-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 10/17/2022] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Porcine cytomegalovirus (PCMV) is a porcine roseolovirus (PCMV/PRV) which is widely distributed in pigs. Transmission of PCMV/PRV in preclinical xenotransplantations was shown to significantly reduce the survival time of the pig transplants in non-human primates. PCMV/PRV was also transmitted in the first transplantation of a pig heart into a human patient. To analyze how PCMV/PRV could be introduced into pig breeds, especially considering cloned transgenic pigs, and subsequently spread in breeding facilities, we screened ovaries and derived materials which are used to perform somatic cell nuclear transfer (SCNT). METHODS DNA was isolated from ovarian tissues, follicular fluids, oocytes with cumulus cells, denuded oocytes and parthenotes. A real-time PCR with PCMV/PRV-specific primers and a probe was performed to detect PCMV/PRV. Furthermore, a Western blot assay using a recombinant fragment of the gB protein of PCMV/PRV was performed to screen for virus-specific antibodies in the follicular fluids. RESULTS PCMV/PRV was found by real-time PCR in ovarian tissues, in the follicular fluid and in oocytes. In parthenotes the virus could not be detected, most-likely due to the low amount of DNA used. By Western blot assay specific antibodies against PCMV/PRV were found in 19 of 20 analyzed follicular fluids. CONCLUSION PCMV/PRV was found in ovarian tissues, in the follicular fluids and also in denuded oocytes, indicating that the virus is present in the animals of which the oocytes were taken from. Despite several washing steps of the denuded oocytes, which are subsequently used for microinjection or SCNT, the virus could still be detected. Therefore, the virus could infect oocytes during genetic modifications or stay attached to the surface of the oocytes, potentially infecting SCNT recipient animals.
Collapse
Affiliation(s)
- Sabrina Hansen
- grid.14095.390000 0000 9116 4836Institute of Virology, Free University Berlin, Berlin, Germany
| | - Konrad Fischer
- grid.6936.a0000000123222966Chair of Animal Biotechnology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Freising, Germany
| | - Ludwig Krabben
- grid.14095.390000 0000 9116 4836Institute of Virology, Free University Berlin, Berlin, Germany
| | - Alexander Rinke Carrapeiro
- grid.6936.a0000000123222966Chair of Animal Biotechnology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Freising, Germany
| | - Bernhard Klinger
- grid.6936.a0000000123222966Chair of Animal Biotechnology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Freising, Germany
| | - Angelika Schnieke
- grid.6936.a0000000123222966Chair of Animal Biotechnology, TUM School of Life Sciences Weihenstephan, Technical University Munich, Freising, Germany
| | - Benedikt Kaufer
- grid.14095.390000 0000 9116 4836Institute of Virology, Free University Berlin, Berlin, Germany
| | - Joachim Denner
- Institute of Virology, Free University Berlin, Berlin, Germany.
| |
Collapse
|
10
|
Fares-Gusmao R, Jiang Z, Subramaniam S, Visser BJ, Scott A, Ishida Y, Saito T, Baylis SA, McGivern DR. Development and characterization of secondary standards for nucleic acid amplification technology (NAAT) assays for detection of hepatitis E virus. J Clin Virol 2022; 157:105325. [PMID: 36395548 PMCID: PMC9714074 DOI: 10.1016/j.jcv.2022.105325] [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] [Academic Contribution Register] [Received: 08/02/2022] [Revised: 10/17/2022] [Accepted: 11/04/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND To harmonize assays for detection of HEV RNA, a World Health Organization International Standard (WHO IS) was established. The WHO IS represents the highest order standard for HEV RNA but is limited in quantity. Secondary standards are needed to limit the use of WHO IS and minimize the need to replace it. OBJECTIVE Establish secondary standards for HEV NAAT assays and to calibrate these against the WHO IS. METHODS Stocks of genotype 3 HEV were prepared using both cell lysates and cell culture supernatants to produce non-enveloped and quasi-enveloped virus stocks, respectively. Both stocks were heat-inactivated, diluted in negative human plasma, and lyophilized to produce two candidate secondary standards: HEV-RR (non-enveloped virus) and HEV-RR.1 (quasi-enveloped virus). Both candidate standards were characterized and calibrated against the WHO IS for HEV RNA in an international collaborative study. RESULTS The collaborative study returned a total of 15 data sets, with different RNA extraction and amplification methods. The estimated mean values relative to the WHO IS (250,000 IU/ml) are 229,000 IU/ml and 355,000 IU/ml for HEV-RR and HEV-RR.1, respectively. CONCLUSION We have established two secondary standards for HEV RNA calibrated against the WHO IS. These standards are non-infectious and stable under different storage temperatures.
Collapse
Affiliation(s)
- Rafaelle Fares-Gusmao
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA
| | - Zhen Jiang
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA
| | - Sakthivel Subramaniam
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA
| | - Bryan J Visser
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA
| | - Alysia Scott
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA
| | - Yuji Ishida
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.; Research and Development Department, PhoenixBio, Co., Ltd, Kagamiyama, Higashi-Hiroshima, Hiroshima, Japan
| | - Takeshi Saito
- Department of Medicine, Division of Gastrointestinal and Liver Diseases, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.; Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA
| | - Sally A Baylis
- Viral Safety Section, Paul-Ehrlich-Institut, Langen, Germany
| | - David R McGivern
- Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, Maryland, USA..
| |
Collapse
|
11
|
Pellerin M, Trabucco B, Capai L, Laval M, Maestrini O, Jori F, Falchi A, Doceul V, Charrier F, Casabianca F, Pavio N. Low prevalence of hepatitis E virus in the liver of Corsican pigs slaughtered after 12 months despite high antibody seroprevalence. Transbound Emerg Dis 2022; 69:e2706-e2718. [PMID: 35689821 PMCID: PMC9796636 DOI: 10.1111/tbed.14621] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/10/2022] [Revised: 05/20/2022] [Accepted: 06/03/2022] [Indexed: 01/01/2023]
Abstract
Hepatitis E virus (HEV) infection can be acute and benign or evolve to chronic hepatitis with rapid progression toward cirrhosis or liver failure in humans. Hence, hepatitis E (HE) disease is a major public health concern. In countries where pig populations are highly contaminated with HEV, human cases of HE are mainly foodborne, occurring frequently after consumption of raw or undercooked pork products or liver. Among factors associated to the presence of HEV in pork livers from intensive rearing systems, early slaughter (≤6 months) seems to be major. In Corsica, local pigs are raised in extensive farming systems and slaughtered after 12 months. To evaluate if slaughter of pigs over 12 months reduces the risk of HEV presence in livers, 1197 liver samples were randomly collected in 2 Corsican slaughterhouses. Presence of HEV RNA was detected in liver and HEV seroprevalence was determined in paired serum. The sampling included 1083 livers from animals between 12 and 48 months and 114 livers from animals <12 months. The samples were predominantly from semi-extensive and extensive farms (n = 1154). Estimated HEV seroprevalence was high, that is, >88%, and HEV RNA prevalence in adult pig livers (>12 months old) was low, that is, 0.18%. However, in livers from younger animals (<12 months), including piglets below 6 months old, 5.3% (6/114) of the samples were positive for HEV RNA. Sequences recovered from positive livers belonged to HEV genotype 3c and 3f. The presence of infectious HEV was confirmed in two livers by the detection of HEV replication in HepaRG cell cultures. Thus, this study demonstrates the low prevalence of HEV in livers of pigs over 12 months, even in farms with high HEV circulation. This observation may open new perspectives on the preferential use of livers from animals older than 12 months in raw pork liver products.
Collapse
Affiliation(s)
- Marie Pellerin
- UMR VirologieANSES, INRAE, ENVALaboratoire de Santé AnimaleMaisons‐AlfortFrance
| | | | - Lisandru Capai
- Laboratoire de VirologieUniversité de Corse Pasquale PaoliUR BIOSCOPE 7310CorteFrance,Institute of Virology, University of Charité BerlinAG Junglen10117BerlinGermany
| | | | | | - Ferran Jori
- UMR ASTRE (Animaux, Santé, Territoire, Risques et Ecosystèmes), CIRADINRAEUniversité de MontpellierCampus International de BaillarguetMontpellierFrance
| | - Alessandra Falchi
- Laboratoire de VirologieUniversité de Corse Pasquale PaoliUR BIOSCOPE 7310CorteFrance
| | - Virginie Doceul
- UMR VirologieANSES, INRAE, ENVALaboratoire de Santé AnimaleMaisons‐AlfortFrance
| | - François Charrier
- UR SELMET‐LRDEINRAECorteFrance,UMR LISIS, Université Gustave EiffelINRAECNRSMarne‐la‐ValléeFrance
| | | | - Nicole Pavio
- UMR VirologieANSES, INRAE, ENVALaboratoire de Santé AnimaleMaisons‐AlfortFrance
| |
Collapse
|
12
|
Fontana RJ, Engle RE, Hayashi PH, Gu J, Kleiner DE, Nguyen H, Barnhart H, Hoofnagle JH, Farci P. Incidence of Hepatitis E Infection in American Patients With Suspected Drug-Induced Liver Injury Is Low and Declining: The DILIN Prospective Study. Am J Gastroenterol 2022; 117:1462-1470. [PMID: 35973149 PMCID: PMC9437122 DOI: 10.14309/ajg.0000000000001869] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 02/25/2022] [Accepted: 06/07/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Hepatitis E virus (HEV) infection rarely causes icteric hepatitis, yet 10%-40% of adult Americans have serological evidence of previous infection. The aim of this study was to investigate the incidence, presentation, and outcome of acute and previous HEV infection in a large cohort of patients with suspected drug-induced liver injury (DILI). METHODS Serum samples from 2012 patients enrolled in the DILI Network were tested for anti-HEV immunoglobulin G (IgG). Those with detectable anti-HEV IgG underwent testing for anti-HEV IgM; those with detectable anti-HEV immunoglobulin m (IgM) were tested for HEV RNA. RESULTS Anti-HEV IgG was detected in 407 (20%) patients and associated with increasing subject age and earlier year of enrollment. The median age of seropositive subjects was more than a decade higher than seronegative subjects (59.8 vs 48.7 years). The overall prevalence of anti-HEV declined from 22% (2004-2011) to 18% (2012-2019), suggestive of a cohort effect. The frequency of acute hepatitis E (median ALT = 1231 IU/L) also decreased from 3% (2004-2008) to 1.2% (2009-2013) to 0.6% (2014-2019). These results suggest that acute HEV infection is usually subclinical and was much more frequent in this cohort before 2004. DISCUSSION Acute HEV infection accounts for less than 1% of suspected American DILI cases and is more frequent in older men. Previous HEV infection is also most commonly seen in older individuals. Clinicians should consider testing for unsuspected acute HEV infection in older adult patients with acute hepatocellular DILI and jaundice.
Collapse
Affiliation(s)
- Robert John Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA
| | - Ronald E Engle
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Paul H Hayashi
- Food and Drug Administration, Silver Spring, Maryland, USA
| | - Jiezhun Gu
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - David E Kleiner
- Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hahn Nguyen
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| | - Huiman Barnhart
- Duke Clinical Research Institute, Durham, North Carolina, USA
| | - Jay H Hoofnagle
- Department of Medicine, Ohio State University, Columbus, Ohio, USA
- National Institute of Diabetes and Digestive and Kidney-Diseases, Bethesda, Maryland, USA
| | - Patrizia Farci
- Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, NIAID, Bethesda, Maryland, USA
| |
Collapse
|
13
|
Ahmad T, Jin H, Dhama K, Yatoo MI, Tiwari R, Bilal M, Dhawan M, Emran TB, Alestad JH, Alhani HM, BinKhalaf HK, Rabaan AA. Hepatitis E virus in pigs and the environment: An updated review of public health concerns. NARRA J 2022; 2:e78. [PMID: 38449702 PMCID: PMC10914032 DOI: 10.52225/narra.v2i2.78] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 04/19/2022] [Accepted: 07/22/2022] [Indexed: 09/01/2023]
Abstract
Hepatitis E virus (HEV) is an important public health problem and is responsible for both acute and chronic viral hepatitis. Public health implications of HEV are derived from its transmission route, either water-borne or food-borne, and its zoonotic potential. Not only in developing countries, but HEV cases are also found in a high number in developed countries. The spread of HEV to the environment might pollute surface waters, which could act as the source of infection for both humans and animals. Identification of the virus in animal products suggests the circulation of HEV within water and food chains. High seroprevalence and circulation of HEV in livestock, in particular pigs, as well as in environmental samples warrants further investigation into pig markets. HEV virulence in different environments and meat supply chains could shed light on the possible sources of infection in humans and the degree of occupational risk. The purpose of this review is to discuss HEV infections with an emphasis on livestock- and environment-related risk factors, and food-borne, water-borne, and zoonotic transmissions.
Collapse
Affiliation(s)
- Tauseef Ahmad
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing,Chinas
| | - Hui Jin
- Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing,Chinas
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly, Uttar Pradesh, India
| | - Mohd. Iqbal Yatoo
- Sher-E-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Srinagar, Jammu and Kashmir, Indias
| | - Ruchi Tiwari
- Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go Anusandhan Sansthan (DUVASU), Mathura, India
| | - Muhammad Bilal
- School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian, China
| | - Manish Dhawan
- Department of Microbiology, Punjab Agricultural University, Ludhiana, India
- The Trafford Group of Colleges, Manchester, United Kingdom
| | - Talha B. Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
| | - Jeehan H. Alestad
- Immunology and Infectious Microbiology, Glasgow, United Kingdom
- Collage of medicine, Microbiology, Jabriya, Kuwait
- Kuwait Chair Madam in Antimicrobial Resistance Committee, Alternative Permanent Representative of Kuwait to the United Nation Agencies, Rome, Italys
| | - Hatem M. Alhani
- Department of Pediatric Infectious Disease, Maternity and Children Hospital, Dammam, Saudi Arabia
- Department of Infection Control, Maternity and Children Hospital, Dammam, Saudi Arabia
- Department of Preventive Medicine and Infection Prevention and Control, Directorate of Ministry of Health, Eastern Region, Dammam, Saudi Arabia
| | - Habib K. BinKhalaf
- Department of Molecular Laboratory, King Fahad Hospital, Hofuf, Saudi Arabia
| | - Ali A. Rabaan
- Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Department of Public Health and Nutrition, The University of Haripur, Haripur, Pakistan
| |
Collapse
|
14
|
Boxman ILA, Verhoef L, Dop PY, Vennema H, Dirks RAM, Opsteegh M. High prevalence of acute hepatitis E virus infection in pigs in Dutch slaughterhouses. Int J Food Microbiol 2022; 379:109830. [PMID: 35908493 DOI: 10.1016/j.ijfoodmicro.2022.109830] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/21/2021] [Revised: 05/19/2022] [Accepted: 07/03/2022] [Indexed: 11/28/2022]
Abstract
Hepatitis E is caused by hepatitis E virus (HEV), one of the causes of acute viral hepatitis. Domestic pigs are considered as the main reservoir of HEV-3. The recently reported high prevalence of HEV in liver- and meat products on the Dutch market warranted a cross-sectional prevalence study on HEV infection among 5-6 months old pigs slaughtered in the Netherlands (n = 250). For this, liver, caecum content and blood samples were analyzed for the presence of genomic HEV RNA by RT-PCR. In addition, a serological test was performed to detect HEV IgG. Background information was retrieved on the corresponding farms to evaluate potential risk factors for HEV at pig slaughter age. HEV IgG was detected in sera from 167 pigs (67.6 %). HEV RNA was detected in 64 (25.6 %) caecum content samples, in 40 (16.1 %) serum samples and in 25 (11.0 %) liver samples. The average level of viral contamination in positive samples was log10 4.6 genome copies (gc)/g (range 3.0-8.2) in caecum content, log10 3.3 gc/ml (range 2.4-5.9) in serum and log10 3.2 gc/0.1 g (range 1.7-6.2) in liver samples. Sequence analyses revealed HEV-3c only. Ten times an identical strain was detected in two or three samples obtained from the same pig. Each animal in this study however appeared to be infected with a unique strain. The presence of sows and gilts and welfare rating at the farm of origin had a significant effect (p < 0.05) on the distribution over the four groups representing different stages of HEV infection based on IgG or RNA in caecum and/or serum. The observed proportion of tested pigs with viremia (16 %) was higher than in other reported studies and was interestingly often observed in combination with a high number of HEV genome copies in liver and caecum content as detected by RT-qPCR. Data provided will be useful for risk assessment for food safety of pork products, will provide baseline data for future monitoring of HEV infections in pigs and new thoughts for mitigation strategies.
Collapse
Affiliation(s)
- Ingeborg L A Boxman
- WFSR, Wageningen Food Safety Research, Wageningen University and Research, Mailbox 230, 6700 AE Wageningen, the Netherlands.
| | - Linda Verhoef
- NVWA, Netherlands Food and Consumer Product Safety Authority, Utrecht, the Netherlands
| | - Petra Y Dop
- NVWA, Netherlands Food and Consumer Product Safety Authority, Utrecht, the Netherlands
| | - Harry Vennema
- RIVM, National Institute of Public Health and the Environment, Bilthoven, the Netherlands
| | - René A M Dirks
- WFSR, Wageningen Food Safety Research, Wageningen University and Research, Mailbox 230, 6700 AE Wageningen, the Netherlands
| | - Marieke Opsteegh
- RIVM, National Institute of Public Health and the Environment, Bilthoven, the Netherlands
| |
Collapse
|
15
|
The first evidence of zoonotic hepatitis E virus (HEV) exposure in domestic cats in Türkiye. Comp Immunol Microbiol Infect Dis 2022; 86:101820. [DOI: 10.1016/j.cimid.2022.101820] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/19/2022] [Revised: 05/03/2022] [Accepted: 05/09/2022] [Indexed: 11/18/2022]
|
16
|
Denner J. Risk of pathogenic virus transmission by somatic cell nuclear transfer (SCNT): implications for xenotransplantation. Biol Reprod 2022; 107:717-722. [PMID: 35699429 DOI: 10.1093/biolre/ioac120] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 02/14/2022] [Revised: 05/13/2022] [Accepted: 06/13/2022] [Indexed: 11/13/2022] Open
Abstract
Using somatic cell nuclear transfer (SCNT) for the generation of cloned and transgenic animals bears the risk of transmission of viruses, either by the oocyte or by the introduced donor cell. There is evidence that the zona pellucida (ZP) surrounding the oocyte prevents virus infection, however, virus infections despite intact ZP were reported. Furthermore, the protective ZP has to be penetrated in order to place the somatic cell in the oocyte's perivitelline space during SCNT. Transmission of viruses represents also a severe problem during in vitro fertilization (IVF). Genetically modified and IVF-produced pigs serve as an important biomedical model for numerous diseases and it is important to evaluate whether infections of the model animals can falsify the research data. Of special significance is this topic in the case of xenotransplantation using genetically modified pigs as donor animals, because transmission of porcine viruses may be harmful for the human recipient. This was repeatedly demonstrated in preclinical pig to non-human primate trials. Therefore, donor pigs, oocytes used for SCNT and genetically modified donor cells should be screened for potentially zoonotic viruses when creating genetically modified pigs designed for xenotransplantation.
Collapse
|
17
|
Doerksen T, Christensen T, Lu A, Noll L, Bai J, Henningson J, Palinski R. Assessment of Porcine Rotavirus-associated virome variations in pigs with enteric disease. Vet Microbiol 2022; 270:109447. [PMID: 35561657 DOI: 10.1016/j.vetmic.2022.109447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 01/26/2022] [Revised: 04/14/2022] [Accepted: 04/23/2022] [Indexed: 11/29/2022]
|
18
|
Damiris K, Aghaie Meybodi M, Niazi M, Pyrsopoulos N. Hepatitis E in immunocompromised individuals. World J Hepatol 2022; 14:482-494. [PMID: 35582299 PMCID: PMC9055194 DOI: 10.4254/wjh.v14.i3.482] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Academic Contribution Register] [Received: 10/12/2021] [Revised: 12/15/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatitis E virus (HEV) originally identified as a cause of acute icteric hepatitis in developing countries has grown to be a cause of zoonotic viral hepatitis in developed countries such as the United States. While there are eight identified genotypes to date, genotype 1 (HEV1), HEV2, HEV3, HEV4 are the most common to infect humans. HEV1 and HEV2 are most common in developing countries including Latina America, Africa and Asia, and are commonly transmitted through contaminated water supplies leading to regional outbreaks. In contrast HEV3 and HEV4 circulate freely in many mammalian animals and can lead to occasional transmission to humans through fecal contamination or consumption of undercooked meat. The incidence and prevalence of HEV in the United States is undetermined given the absence of FDA approved serological assays and the lack of commercially available testing. In majority of cases, HEV infection is a self-limiting hepatitis requiring only symptomatic treatment. However, this is not the case in immunocompromised individuals, including those that have undergone solid organ or stem cell transplantation. In this subset of patients, chronic infection can be life threatening as hepatic insult can lead to inflammation and fibrosis with subsequent cirrhosis and death. The need for re-transplantation as a result of post-transplant hepatitis is of great concern. In addition, there have been many reported incidents of extrahepatic manifestations, for which the exact mechanisms remain to be elucidated. The cornerstone of treatment in immunocompromised solid organ transplant recipients is reduction of immunosuppressive therapies, while attempting to minimize the risk of organ rejection. Subsequent treatment options include ribavirin, and pegylated interferon alpha in those who have demonstrated ribavirin resistance. Further investigation assessing safety and efficacy of anti-viral therapy is imperative given the rising global health burden. Given this concern, vaccination has been approved in China with other investigations underway throughout the world. In this review we introduce the epidemiology, diagnosis, clinical manifestations, and treatment of HEV, with emphasis on immunocompromised individuals in the United States.
Collapse
Affiliation(s)
- Konstantinos Damiris
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mohamad Aghaie Meybodi
- Department of Medicine, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Mumtaz Niazi
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Department of Medicine - Gastroenterology and Hepatology, Rutgers - New Jersey Medical School, Newark, NJ 07103, United States
| |
Collapse
|
19
|
Schommer SK, Harrison N, Linville M, Samuel MS, Hammond SL, Wells KD, Prather RS. Serologic titers to Leptospira in vaccinated pigs and interpretation for surveillance. PLoS One 2021; 16:e0260052. [PMID: 34784395 PMCID: PMC8594815 DOI: 10.1371/journal.pone.0260052] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 08/09/2021] [Accepted: 10/29/2021] [Indexed: 11/18/2022] Open
Abstract
Diagnosis and surveillance of pathogenic Leptospira is difficult as organisms may be intermittently shed and in small numbers. Therefore, serologic testing by the microscopic agglutination test (MAT) is the primary screening method for leptospirosis. While a MAT titer ≥1:100 is considered to be a positive result, interpretation is complicated by the use of commercial vaccines in pigs. Most guidelines for interpretation of MAT titers in pigs were published in the 1970’s and 1980’s, prior to the development of the current multivalent vaccines. We evaluated MAT titers in routinely vaccinated healthy research pigs compared to their unvaccinated cohorts. Our study confirmed previous reports that the Pomona serovar elicits minimal antibody response even after a second booster 6 months after initial vaccination. However, MAT titers of ≥1:3,200 were detected as early as 4 weeks post initial vaccination for serovars Bratislava and Icterohaemorrhagiae and remained as high as ≥1:1,600 prior to booster at 24 weeks post vaccination. Our study determined that high levels of MAT titers can occur from vaccination alone and high titers are not necessarily indicative of infection. Therefore, the interpretation of MAT titers as indicators of Leptospira infection should be readdressed.
Collapse
Affiliation(s)
- Susan K. Schommer
- National Swine Resource and Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America
- * E-mail:
| | - Nicholas Harrison
- Office of Animal Resources, University of Missouri, Columbia, Missouri, United States of America
| | - Michael Linville
- Office of Animal Resources, University of Missouri, Columbia, Missouri, United States of America
| | - Melissa S. Samuel
- National Swine Resource and Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America
| | - Sabrina L. Hammond
- National Swine Resource and Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America
| | - Kevin D. Wells
- National Swine Resource and Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America
| | - Randall S. Prather
- National Swine Resource and Research Center, Division of Animal Sciences, University of Missouri, Columbia, Missouri, United States of America
| |
Collapse
|
20
|
Bigoraj E, Paszkiewicz W, Rzeżutka A. Porcine Blood and Liver as Sporadic Sources of Hepatitis E Virus (HEV) in the Production Chain of Offal-Derived Foodstuffs in Poland. FOOD AND ENVIRONMENTAL VIROLOGY 2021; 13:347-356. [PMID: 33891305 PMCID: PMC8379118 DOI: 10.1007/s12560-021-09475-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 10/08/2020] [Accepted: 04/09/2021] [Indexed: 05/11/2023]
Abstract
Pig's blood and liver are valuable edible slaughter by-products which are also the major ingredients of offal-derived foodstuffs. The aim of the study was an evaluation of the occurrence of hepatitis E virus (HEV) and porcine adenovirus (pAdV) as an index virus of faecal contamination in pig's blood and liver for human consumption. In total, 246 samples of retail liver (n = 100) and pooled pig's blood (n = 146) were analysed for the presence of HEV and pAdV. Blood samples were individually collected from 1432 pigs at slaughter age. Viral genomic material, including RNA of a sample process control virus was isolated from food samples using a QIAamp® Viral RNA Mini Kit. Virus-specific IAC-controlled real-time PCR methods were used for detection of target viruses. HEV RNA was found in 6 (2.4%; 95% CI: 0.9-5.2) out of 246 samples of tested foodstuffs. The virus was detected in pig's blood (3.4%; 95% CI: 1.1-7.8) and liver (1.0%; 95% CI: 0.0-5.0) with no significant differences observed in the frequency of its occurrence between the two by-products (t = 1.33; p = 0.182 > 0.05); however PAdV was detected more frequently in pig's blood than in liver (t = 4.65; p = 0.000 < 0.05). The HEV strains belonged to the 3f and 3e subtype groups and the pAdV strains were assigned to serotype 5. PAdV was detected in pigs regardless of the farm size from which they originated. The number of animals raised on the farm (the farm size) had no influence on the occurrence of HEV or pAdV infections in pigs (F = 0.81, p = 0.447 > 0.05 for HEV; F = 0.42, p = 0.655 > 0.05 for pAdV). Although HEV was detected in pig's offal only sporadically, consumers cannot treat its occurrence with disregard as it demonstrates that HEV-contaminated pig tissues can enter the food chain.
Collapse
Affiliation(s)
- E Bigoraj
- Department of Food and Environmental Virology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100, Puławy, Poland
| | - W Paszkiewicz
- Department of Food Hygiene of Animal Origin, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, ul. Akademicka 12, 20-950, Lublin, Poland
| | - A Rzeżutka
- Department of Food and Environmental Virology, National Veterinary Research Institute, Al. Partyzantów 57, 24-100, Puławy, Poland.
| |
Collapse
|
21
|
Treagus S, Wright C, Baker-Austin C, Longdon B, Lowther J. The Foodborne Transmission of Hepatitis E Virus to Humans. FOOD AND ENVIRONMENTAL VIROLOGY 2021; 13:127-145. [PMID: 33738770 PMCID: PMC8116281 DOI: 10.1007/s12560-021-09461-5] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Academic Contribution Register] [Received: 10/20/2020] [Accepted: 01/16/2021] [Indexed: 05/04/2023]
Abstract
Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food.
Collapse
Affiliation(s)
- Samantha Treagus
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK.
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK.
| | | | - Craig Baker-Austin
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
| | - Ben Longdon
- Biosciences, College of Life and Environmental Sciences, University of Exeter, Penryn Campus, Penryn, Cornwall, UK
| | - James Lowther
- Centre for Environment Fisheries and Aquaculture Science, Barrack Road, Weymouth, Dorset, DT4 8UB, UK
| |
Collapse
|
22
|
Hepatitis E Virus RNA Presence in Wild Boar Carcasses at Slaughterhouses in Italy. Animals (Basel) 2021; 11:ani11061624. [PMID: 34072795 PMCID: PMC8230283 DOI: 10.3390/ani11061624] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/05/2021] [Revised: 05/27/2021] [Accepted: 05/28/2021] [Indexed: 12/26/2022] Open
Abstract
Simple Summary Hepatitis E virus (HEV) is a worldwide diffused pathogen responsible for acute hepatitis of humans. Transmission of the pathogen is mostly related to the consumption of contaminated food and water. Although initially the disease was contained in developing countries, in recent years autochthonous infections have been reported in several industrialised countries. A different epidemiological pattern of transmission has been highlighted; while in Africa and Asia transmission is mainly due to waterborne outbreaks caused by low sanitation standards, in Europe and other industrialised countries, the disease has mainly spread due to consumption of raw or undercooked meat and seafood. Although HEV has been identified in several domestic and wild animal species, pigs and wild boar, appear to play a distinct role mainly acting as a reservoir of the pathogen. In this study, we monitored the presence of HEV in carcasses and livers of wild boar sampled in Tuscany at the slaughterhouse following hunting activities. Our data indicate the presence of the pathogen in the liver and the carcasses, suggesting cross-contamination. This evidence highlights the importance of maintaining safety control measures to avoid the spreading of HEV infection. Abstract Hepatitis E virus (HEV) is a waterborne and foodborne pathogen largely spread around the world. HEV is responsible for acute hepatitis in humans and it is also diffused in domestic and wild animals. In particular, domestic pigs represent the main reservoir of the infection and particular attention should be paid to the consumption of raw and undercooked meat as a possible zoonotic vehicle of the pathogen. Several studies have reported the presence of HEV in wild boar circulating in European countries with similar prevalence rates. In this study, we evaluated the occurrence of HEV in wild boar hunted in specific areas of Tuscany. Sampling was performed by collecting liver samples and also by swabbing the carcasses at the slaughterhouses following hunting activities. Our data indicated that 8/67 (12%) of liver samples and 4/67 (6%) of swabs were positive for HEV RNA. The presence of HEV genome on swabs indicates the possible cross-contamination of carcass surfaces during slaughtering procedures. Altogether, our data indicated that it is essential to promote health education programmes for hunters and consumers to limit the diffusion of the pathogen to humans.
Collapse
|
23
|
Crotta M, Lavazza A, Mateus A, Guitian J. Viraemic pigs entering the food chain are the most likely source of hepatitis E virus (HEV) in pork meat: Modelling the fate of HEV during slaughtering of pigs. Food Control 2021. [DOI: 10.1016/j.foodcont.2020.107662] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Indexed: 12/25/2022]
|
24
|
Hepatitis E Virus Occurrence in Pigs Slaughtered in Italy. Animals (Basel) 2021; 11:ani11020277. [PMID: 33499160 PMCID: PMC7911034 DOI: 10.3390/ani11020277] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 12/18/2020] [Revised: 01/19/2021] [Accepted: 01/19/2021] [Indexed: 12/11/2022] Open
Abstract
Simple Summary Hepatitis E is now recognized as an emerging zoonotic disease in Europe caused by an RNA virus (HEV) and foodborne is the main route of transmission. Human cases have been linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. The zoonotic genotype HEV-3 is widespread in pigs at farm level but little information is available on the occurrence of HEV-positive pigs at the slaughterhouse. The aim of this study was to investigate the prevalence of HEV-positive pigs during slaughtering, to understand which biological samples (feces and organs) were more frequently HEV positive. Our results showed that pigs positive for HEV can be slaughtered and that the percentage of positive animals depends on the age of animals. The other main result is the presence of the virus in the plasma of animals, which may contribute to the contamination of meat (muscle). Nevertheless, muscles are rarely contaminated by HEV-RNA compared to liver, which is the organ of replication. Abstract In Europe, foodborne transmission has been clearly associated to sporadic cases and small clusters of hepatitis E in humans linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. In Europe, zoonotic HEV-genotype 3 strains are widespread in pig farms but little information is available on the prevalence of HEV positive pigs at slaughterhouse. In the present study, the prevalence of HEV-RNA positive pigs was assessed on 585 animals from 4 abattoirs located across Italy. Twenty-one pigs (3.6%) tested positive for HEV in either feces or liver by real-time RT-PCR. In these 21 pigs, eight diaphragm muscles resulted positive for HEV-RNA. Among animals collected in one abattoir, 4 out of 91 plasma tested positive for HEV-RNA. ELISA tests for the detection of total antibodies against HEV showed a high seroprevalence (76.8%), confirming the frequent exposure of pigs to the virus. The phylogenetic analyses conducted on sequences of both ORF1 and ORF2 fragments, shows the circulation of HEV-3c and of a novel unclassified subtype. This study provides information on HEV occurrence in pigs at the slaughterhouse, confirming that muscles are rarely contaminated by HEV-RNA compared to liver, which is the most frequently positive for HEV.
Collapse
|
25
|
Veronesi R, Morach M, Hübschke E, Bachofen C, Stephan R, Nüesch‐Inderbinen M. Seroprevalence of hepatitis E virus in dogs in Switzerland. Zoonoses Public Health 2020; 68:8-11. [DOI: 10.1111/zph.12779] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 05/06/2020] [Revised: 08/26/2020] [Accepted: 10/18/2020] [Indexed: 01/14/2023]
Affiliation(s)
- Rebecca Veronesi
- Institute for Food Safety and Hygiene Vetsuisse Faculty University of Zurich Zurich Switzerland
| | - Marina Morach
- Institute for Food Safety and Hygiene Vetsuisse Faculty University of Zurich Zurich Switzerland
| | - Ella Hübschke
- Institute for Food Safety and Hygiene Vetsuisse Faculty University of Zurich Zurich Switzerland
| | - Claudia Bachofen
- Institute of Virology Vetsuisse Faculty University of Zurich Zurich Switzerland
| | - Roger Stephan
- Institute for Food Safety and Hygiene Vetsuisse Faculty University of Zurich Zurich Switzerland
| | | |
Collapse
|
26
|
Wang B, Meng XJ. Hepatitis E virus: host tropism and zoonotic infection. Curr Opin Microbiol 2020; 59:8-15. [PMID: 32810801 DOI: 10.1016/j.mib.2020.07.004] [Citation(s) in RCA: 76] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 04/10/2020] [Revised: 07/14/2020] [Accepted: 07/16/2020] [Indexed: 02/06/2023]
Abstract
Hepatitis E virus (HEV), the causative agent of hepatitis E, is an understudied but important pathogen. HEV typically causes self-limiting acute viral hepatitis, however chronic infection with neurological and other extrahepatic manifestations has increasingly become a significant clinical problem. The discovery of swine HEV from pigs and demonstration of its zoonotic potential led to the genetic identification of very diverse HEV strains from more than a dozen other animal species. HEV strains from pig, rabbit, deer, camel, and rat have been shown to cross species barriers and infect humans. Zoonotic HEV infections through consumption of raw or undercooked animal meat or direct contact with infected animals have been reported. The discovery of a large number of animal HEV variants does provide an opportunity to develop useful animal models for HEV. In this mini-review, we discuss recent advances in HEV host range, and cross-species and zoonotic transmission.
Collapse
Affiliation(s)
- Bo Wang
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
| |
Collapse
|
27
|
Janahi EM, Parkar SFD, Mustafa S, Eisa ZM. Implications of Hepatitis E Virus in Blood Transfusions, Hemodialysis, and Solid Organ Transplants. MEDICINA (KAUNAS, LITHUANIA) 2020; 56:E206. [PMID: 32344807 PMCID: PMC7279256 DOI: 10.3390/medicina56050206] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Academic Contribution Register] [Received: 03/12/2020] [Revised: 04/19/2020] [Accepted: 04/21/2020] [Indexed: 01/05/2023]
Abstract
Hepatitis E Virus (HEV) is emerging as the primary cause of acute viral hepatitis in humans. The virus is commonly transmitted by the fecal-oral route via contaminated water in endemic regions or through the consumption of inadequately cooked swine products or game meats in industrialized regions. HEV genotypes 1 and 2 are predominantly associated with waterborne transmission in developing countries, whereas HEV3 and HEV4 are mainly zoonotically transmitted in industrialized countries. Seroprevalence in populations determined by detecting anti-HEV antibodies and serum HEV RNA is commonly used to analyze the presence of HEV. Although HEV RNA-based detection is now standardized, there is a lack of agreement between the assaying methods used for gathering seroprevalence data. Since 2004, HEV has been considered as a transmissible infectious agent through blood transfusion. Recent seroprevalence studies in European countries indicate an underestimated risk for blood transfusion and hence warrant testing the blood supply. HEV infection is usually self-limiting and spontaneously cleared. However, in about 60% of recipients of solid organ transplants, HEV progresses to chronic hepatitis. Immunosuppressive drugs such as tacrolimus are a major cause of chronic hepatitis and reducing its dosage results in viral clearance in about 30% of patients. In hemodialysis patients, the parenteral route is implicated as an important mechanism of transmission. In this review, we explore the clinical and epidemiological characteristics of various HEV genotypes in blood donors, hemodialysis patients, and transplant recipients.
Collapse
Affiliation(s)
- Essam M. Janahi
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Saba F. D. Parkar
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Sakina Mustafa
- Department of Biology, College of Science, University of Bahrain, Sakhir 32038, Bahrain; (S.F.D.P.); (S.M.)
| | - Zaki M. Eisa
- The National Center for Disease Prevention and Control, Jazan 82722-2476, Saudi Arabia;
| |
Collapse
|
28
|
Sooryanarain H, Meng XJ. Swine hepatitis E virus: Cross-species infection, pork safety and chronic infection. Virus Res 2020; 284:197985. [PMID: 32333941 DOI: 10.1016/j.virusres.2020.197985] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Academic Contribution Register] [Received: 03/03/2020] [Revised: 04/11/2020] [Accepted: 04/17/2020] [Indexed: 12/12/2022]
Abstract
Swine hepatitis E virus (swine HEV) belongs to the species Orthohepevirus A within the genus Orthohepevirus in the family Hepeviridae. Four different genotypes of swine HEV within the species Orthohepevirus A have been identified so far from domesticated and wild swine population: genotypes 3 (HEV-3) and 4 (HEV-4) swine HEVs are zoonotic and infect humans, whereas HEV-5 and HEV-6 are only identified from swine. As a zoonotic agent, swine HEV is an emerging public health concern in many industrialized countries. Pigs are natural reservoir for HEV, consumption of raw or undercooked pork is an important route of foodborne HEV transmission. Occupational risks such as direct contact with infected pigs also increase the risk of HEV transmission in humans. Cross-species infection of HEV-3 and HEV-4 have been documented under experimental and natural conditions. Both swine HEV-3 and swine HEV-4 infect non-human primates, the surrogates of man. Swine HEV, predominantly HEV-3, can establish chronic infection in immunocompromised patients especially in solid organ transplant recipients. The zoonotic HEV-3, and to lesser extent HEV-4, have also been shown to cause neurological diseases and kidney injury. In this review, we focus on the epidemiology of swine HEV, host and viral determinants influencing cross-species HEV infection, zoonotic infection and its associated pork safety concern, as well as swine HEV-associated chronic infection and neurological diseases.
Collapse
Affiliation(s)
- Harini Sooryanarain
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Xiang-Jin Meng
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
| |
Collapse
|