{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:09:12Z","timestamp":1791662952101,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T00:00:00Z","timestamp":1688688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis of the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17fk0210201"],"award-info":[{"award-number":["JP17fk0210201"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis of the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19fk0210043"],"award-info":[{"award-number":["JP19fk0210043"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis of the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22fk0210075"],"award-info":[{"award-number":["JP22fk0210075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Research Program on Hepatitis of the Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP23fk0210132"],"award-info":[{"award-number":["JP23fk0210132"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans. Pigs are the primary reservoir for zoonotic HEV genotypes 3 and 4 worldwide. This study investigated the infection dynamics and genomic mutations of HEV in domestic pigs on a farrow-to-finish pig farm in Japan between 2012 and 2021. A high prevalence of anti-HEV IgG antibodies was noted among pigs on this farm in 2012, when the survey started, and persisted for at least nine years. During 2012\u20132021, HEV RNA was detected in both serum and fecal samples, indicating active viral replication. Environmental samples, including slurry samples in manure pits, feces on the floor, floor and wall swabs in pens, and dust samples, also tested positive for HEV RNA, suggesting potential sources of infection within the farm environment. Indeed, pigs raised in HEV-contaminated houses had a higher rate of HEV infection than those in an HEV-free house. All 104 HEV strains belonged to subgenotype 3b, showing a gradual decrease in nucleotide identities over time. The 2012 (swEJM1201802S) and 2021 (swEJM2100729F) HEV strains shared 97.9% sequence identity over the entire genome. Importantly, the swEJM2100729F strain efficiently propagated in human hepatoma cells, demonstrating its infectivity. These findings contribute to our understanding of the prevalence, transmission dynamics, and genetic characteristics of HEV in domestic pigs, emphasizing the potential risks associated with HEV infections and are crucial for developing effective strategies to mitigate the risk of HEV infection in both animals and humans.<\/jats:p>","DOI":"10.3390\/v15071516","type":"journal-article","created":{"date-parts":[[2023,7,10]],"date-time":"2023-07-10T00:45:37Z","timestamp":1688949937000},"page":"1516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Infection Dynamics and Genomic Mutations of Hepatitis E Virus in Naturally Infected Pigs on a Farrow-to-Finish Farm in Japan: A Survey from 2012 to 2021"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-9318","authenticated-orcid":false,"given":"Masaharu","family":"Takahashi","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Kunita","sequence":"additional","affiliation":[{"name":"Center for Experimental Medicine, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Nishizawa","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-5440","authenticated-orcid":false,"given":"Hiroshi","family":"Ohnishi","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7401-979X","authenticated-orcid":false,"given":"Putu Prathiwi","family":"Primadharsini","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8944-713X","authenticated-orcid":false,"given":"Shigeo","family":"Nagashima","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3419-6297","authenticated-orcid":false,"given":"Kazumoto","family":"Murata","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0827-0964","authenticated-orcid":false,"given":"Hiroaki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Infection and Immunity, Jichi Medical University School of Medicine, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","article-title":"Hepatitis E virus infection","volume":"3","author":"Kamar","year":"2017","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00822-17","DOI":"10.1128\/JVI.00822-17","article-title":"Characterization of the Quasi-Enveloped Hepatitis E Virus Particles Released by the Cellular Exosomal Pathway","volume":"91","author":"Nagashima","year":"2017","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jhep.2016.02.045","article-title":"Update on hepatitis E virology: Implications for clinical practice","volume":"65","author":"Debing","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8259","DOI":"10.1073\/pnas.89.17.8259","article-title":"Computer-assisted assignment of functional domains in the nonstructural polyprotein of hepatitis E virus: Delineation of an additional group of positive-strand RNA plant and animal viruses","volume":"89","author":"Koonin","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.jceh.2013.05.001","article-title":"Hepatitis E: Molecular virology and pathogenesis","volume":"3","author":"Panda","year":"2013","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1053\/j.gastro.2017.09.020","article-title":"Hepatitis E Virus Lifecycle and Identification of 3 Forms of the ORF2 Capsid Protein","volume":"154","author":"Montpellier","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1073\/pnas.1721345115","article-title":"Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection","volume":"115","author":"Yin","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gouttenoire, J., Pollan, A., Abrami, L., Oechslin, N., Mauron, J., Matter, M., Oppliger, J., Szkolnicka, D., Dao Thi, V.L., and van der Goot, F.G. (2018). Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007471"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"001778","DOI":"10.1099\/jgv.0.001778","article-title":"ICTV Virus Taxonomy Profile: Hepeviridae 2022","volume":"103","author":"Purdy","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/liv.15076","article-title":"Maternal and fetal outcomes of pregnancies complicated by acute hepatitis E and the impact of HIV status: A cross-sectional study in Namibia","volume":"42","author":"Heemelaar","year":"2022","journal-title":"Liver Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a031732","DOI":"10.1101\/cshperspect.a031732","article-title":"Epidemiology of Genotype 1 and 2 Hepatitis E Virus Infections","volume":"9","author":"Nelson","year":"2019","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2015.10.048","article-title":"Chronic Infection With Camelid Hepatitis E Virus in a Liver Transplant Recipient Who Regularly Consumes Camel Meat and Milk","volume":"150","author":"Lee","year":"2016","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1093\/cid\/ciab919","article-title":"Hepatitis E Virus Species C Infection in Humans, Hong Kong","volume":"75","author":"Sridhar","year":"2022","journal-title":"Clin. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.mib.2020.07.004","article-title":"Hepatitis E virus: Host tropism and zoonotic infection","volume":"59","author":"Wang","year":"2021","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1099\/jgv.0.001435","article-title":"Update: Proposed reference sequences for subtypes of hepatitis E virus (species Orthohepevirus A)","volume":"101","author":"Smith","year":"2020","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9860","DOI":"10.1073\/pnas.94.18.9860","article-title":"A novel virus in swine is closely related to the human hepatitis E virus","volume":"94","author":"Meng","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.virusres.2011.01.016","article-title":"From barnyard to food table: The omnipresence of hepatitis E virus and risk for zoonotic infection and food safety","volume":"161","author":"Meng","year":"2011","journal-title":"Virus Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13567-017-0436-3","article-title":"From the epidemiology of hepatitis E virus (HEV) within the swine reservoir to public health risk mitigation strategies: A comprehensive review","volume":"48","author":"Salines","year":"2017","journal-title":"Vet. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"197985","DOI":"10.1016\/j.virusres.2020.197985","article-title":"Swine hepatitis E virus: Cross-species infection, pork safety and chronic infection","volume":"284","author":"Sooryanarain","year":"2020","journal-title":"Virus Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/hepr.12175","article-title":"Features of hepatitis E virus infection in humans and animals in Japan","volume":"44","author":"Takahashi","year":"2014","journal-title":"Hepatol. Res."},{"key":"ref_21","first-page":"271","article-title":"Hepatitis E, 2014\u20132021","volume":"42","author":"Yotsuyanagi","year":"2021","journal-title":"Infect. Agents Surveill. Rep. (IASR)"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.1128\/JCM.01086-07","article-title":"Prolonged fecal shedding of hepatitis E virus (HEV) during sporadic acute hepatitis E: Evaluation of infectivity of HEV in fecal specimens in a cell culture system","volume":"45","author":"Takahashi","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1002\/(SICI)1096-9071(199810)56:2<128::AID-JMV5>3.0.CO;2-A","article-title":"Fecal excretion of a nonenveloped DNA virus (TTV) associated with posttransfusion non-A-G hepatitis","volume":"56","author":"Okamoto","year":"1998","journal-title":"J. Med. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1128\/JCM.40.9.3209-3218.2002","article-title":"Polyphyletic strains of hepatitis E virus are responsible for sporadic cases of acute hepatitis in Japan","volume":"40","author":"Mizuo","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1099\/vir.0.80909-0","article-title":"Correlation between positivity for immunoglobulin A antibodies and viraemia of swine hepatitis E virus observed among farm pigs in Japan","volume":"86","author":"Takahashi","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jviromet.2006.07.004","article-title":"Development and validation of an improved RT-PCR assay with nested universal primers for detection of hepatitis E virus strains with significant sequence divergence","volume":"137","author":"Inoue","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00705-008-0045-6","article-title":"Production of monoclonal antibodies against hepatitis E virus capsid protein and evaluation of their neutralizing activity in a cell culture system","volume":"153","author":"Takahashi","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198645","DOI":"10.1016\/j.virusres.2021.198645","article-title":"Identification of hepatitis E virus in wild sika deer in Japan","volume":"308","author":"Takahashi","year":"2022","journal-title":"Virus Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1006\/bbrc.2001.6088","article-title":"Analysis of the complete genome of indigenous swine hepatitis E virus isolated in Japan","volume":"289","author":"Okamoto","year":"2001","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: Multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1093\/molbev\/msw054","article-title":"MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets","volume":"33","author":"Kumar","year":"2016","journal-title":"Mol. Biol. Evol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.virusres.2012.09.015","article-title":"Molecular analysis of hepatitis E virus from farm rabbits in Inner Mongolia, China and its successful propagation in A549 and PLC\/PRF\/5 cells","volume":"170","author":"Jirintai","year":"2012","journal-title":"Virus Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1099\/vir.0.82535-0","article-title":"Development and evaluation of an efficient cell-culture system for Hepatitis E virus","volume":"88","author":"Tanaka","year":"2007","journal-title":"J. Gen. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1007\/s00705-008-0179-6","article-title":"Monoclonal antibodies raised against the ORF3 protein of hepatitis E virus (HEV) can capture HEV particles in culture supernatant and serum but not those in feces","volume":"153","author":"Takahashi","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.meegid.2014.06.024","article-title":"Hepeviridae: An expanding family of vertebrate viruses","volume":"27","author":"Johne","year":"2014","journal-title":"Infect. Genet. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jviromet.2016.03.004","article-title":"Characterization and epitope mapping of monoclonal antibodies raised against rat hepatitis E virus capsid protein: An evaluation of their neutralizing activity in a cell culture system","volume":"233","author":"Kobayashi","year":"2016","journal-title":"J. Virol. Methods"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Motoya, T., Umezawa, M., Goto, K., Doi, I., Nagata, N., Ikeda, Y., Sakuta, A., Sasaki, N., and Ishii, K. (2019). High prevalence of hepatitis E virus infection among domestic pigs in Ibaraki Prefecture, Japan. BMC Vet. Res., 15.","DOI":"10.1186\/s12917-019-1816-x"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1099\/vir.0.18918-0","article-title":"Swine hepatitis E virus strains in Japan form four phylogenetic clusters comparable with those of Japanese isolates of human hepatitis E virus","volume":"84","author":"Takahashi","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1002\/jmv.21647","article-title":"Long-term shedding of hepatitis E virus in the feces of pigs infected naturally, born to sows with and without maternal antibodies","volume":"82","author":"Kanai","year":"2010","journal-title":"J. Med. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.14202\/vetworld.2021.2936-2940","article-title":"In vitro cytotoxicity and virucidal efficacy of potassium hydrogen peroxymonosulfate compared to quaternary ammonium compound under various concentrations, exposure times and temperatures against African swine fever virus","volume":"14","author":"Sovijit","year":"2021","journal-title":"Vet. World"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40813-021-00189-z","article-title":"Infection dynamics and persistence of hepatitis E virus on pig farms\u2014A review","volume":"7","author":"Meester","year":"2021","journal-title":"Porc. Health Manag."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.vetmic.2008.04.036","article-title":"Hepatitis E virus infection dynamics and organic distribution in naturally infected pigs in a farrow-to-finish farm","volume":"132","author":"Casas","year":"2008","journal-title":"Vet. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ijfoodmicro.2007.03.008","article-title":"Presence of hepatitis E virus in a naturally infected swine herd from nursery to slaughter","volume":"117","author":"Leblanc","year":"2007","journal-title":"Int. J. Food Microbiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/j.meegid.2011.07.009","article-title":"Infection dynamics of hepatitis E virus in naturally infected pigs in a Chinese farrow-to-finish farm","volume":"11","author":"Feng","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1111\/tbed.13224","article-title":"Natural viral co-infections in pig herds affect hepatitis E virus (HEV) infection dynamics and increase the risk of contaminated livers at slaughter","volume":"66","author":"Salines","year":"2019","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Andraud, M., Casas, M., Pavio, N., and Rose, N. (2014). Early-life hepatitis e infection in pigs: The importance of maternally-derived antibodies. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105527"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1051\/vetres\/2010018","article-title":"Zoonotic hepatitis E: Animal reservoirs and emerging risks","volume":"41","author":"Pavio","year":"2010","journal-title":"Vet. Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ianiro, G., Monini, M., Ammendolia, M.G., De Sabato, L., Ostanello, F., Vaccari, G., and Di Bartolo, I. (2023). In Vitro Replication of Swine Hepatitis E Virus (HEV): Production of Cell-Adapted Strains. Animals, 13.","DOI":"10.3390\/ani13020276"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13567-022-01068-3","article-title":"Repeated cross-sectional sampling of pigs at slaughter indicates varying age of hepatitis E virus infection within and between pig farms","volume":"53","author":"Meester","year":"2022","journal-title":"Vet. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Withenshaw, S.M., Grierson, S.S., and Smith, R.P. (2022). Study of Animal Mixing and the Dynamics of Hepatitis E Virus Infection on a Farrow-to-Finish Pig Farm. Animals, 12.","DOI":"10.3390\/ani12030272"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ebiom.2016.07.039","article-title":"Hepatitis E Virus Mutations: Functional and Clinical Relevance","volume":"11","author":"Hoan","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.hepres.2004.04.004","article-title":"Estimation of the mutation rate of hepatitis E virus based on a set of closely related 7.5-year-apart isolates from Sapporo, Japan","volume":"29","author":"Takahashi","year":"2004","journal-title":"Hepatol. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.virusres.2016.07.011","article-title":"Analysis of adaptive mutations selected during the consecutive passages of hepatitis E virus produced from an infectious cDNA clone","volume":"223","author":"Nagashima","year":"2016","journal-title":"Virus Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.virusres.2008.06.005","article-title":"Mutational events during the primary propagation and consecutive passages of hepatitis E virus strain JE03-1760F in cell culture","volume":"137","author":"Lorenzo","year":"2008","journal-title":"Virus Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1016\/0042-6822(92)90933-G","article-title":"Genetic drift of hepatitis C virus during an 8.2-year infection in a chimpanzee: Variability and stability","volume":"190","author":"Okamoto","year":"1992","journal-title":"Virology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sari, G., van de Garde, M.D.B., van Schoonhoven, A., Voermans, J.J.C., van der Eijk, A.A., de Man, R.A., Boonstra, A., Vanwolleghem, T., and Pas, S.D. (2019). Hepatitis E Virus Shows More Genomic Alterations in Cell Culture than In Vivo. Pathogens, 8.","DOI":"10.3390\/pathogens8040255"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00705-011-1153-2","article-title":"A549 and PLC\/PRF\/5 cells can support the efficient propagation of swine and wild boar hepatitis E virus (HEV) strains: Demonstration of HEV infectivity of porcine liver sold as food","volume":"157","author":"Takahashi","year":"2012","journal-title":"Arch. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:07:54Z","timestamp":1760126874000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/7\/1516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,7]]},"references-count":57,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["v15071516"],"URL":"https:\/\/doi.org\/10.3390\/v15071516","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,7]]}}}