1887

Abstract

Infection with hepatitis E virus (HEV) can be clinically inapparent or produce symptoms and signs of hepatitis of varying severity and occasional fatality. This variability in clinical outcomes may reflect differences in host susceptibility or the presence of virally encoded determinants of pathogenicity. Analysis of complete genome sequences supports the division of HEV genotype 3 (HEV-3) variants into three major clades: 3ra comprising HEV isolates from rabbits, and 3efg and 3abchij comprising the corresponding named subtypes derived from humans and pigs. Using this framework, we investigated associations between viral genetic variability of HEV-3 in symptomatic and asymptomatic infections by comparing HEV-3 subgenomic sequences previously obtained from blood donors with those from patients presenting with hepatitis in the UK (54 blood donors, 148 hepatitis patients), the Netherlands (38 blood donors, 119 hepatitis patients), France (24 blood donors, 55 hepatitis patients) and Germany (14 blood donors, 36 hepatitis patients). In none of these countries was evidence found for a significant association between virus variants and patient group (>0.05 Fisher's exact test). Furthermore, within a group of 123 patients in Scotland with clinically apparent HEV infections, we found no evidence for an association between variants of HEV-3 and disease severity or alanine aminotransferase level. The lack of detectable virally encoded determinants of disease outcomes in HEV-3 infection implies a more important role for host factors in its clinical phenotype.

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2015-11-01
2020-01-29
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References

  1. Abe T. , Aikawa T. , Akahane Y. , Arai M. , Asahina Y. , Atarashi Y. , Chayama K. , Harada H. , Hashimoto N. , other authors . ( 2006;). [Demographic, epidemiological, and virological characteristics of hepatitis E virus infections in Japan based on 254 human cases collected nationwide]. Kanzo 47: 384–391 (in Japanese with English abstract).[CrossRef]
    [Google Scholar]
  2. Bouquet J. , Cherel P. , Pavio N. . ( 2012;). Genetic characterization and codon usage bias of full-length Hepatitis E virus sequences shed new lights on genotypic distribution, host restriction and genome evolution. Infect Genet Evol 12: 1842–1853 [CrossRef] [PubMed].
    [Google Scholar]
  3. Bu Q. , Wang X. , Wang L. , Liu P. , Geng J. , Wang M. , Han J. , Zhu Y. , Zhuang H. . ( 2013;). Hepatitis E virus genotype 4 isolated from a patient with liver failure: full-length sequence analysis showing potential determinants of virus pathogenesis. Arch Virol 158: 165–172 [CrossRef] [PubMed].
    [Google Scholar]
  4. Chen X. , Zhang Q. , He C. , Zhang L. , Li J. , Zhang W. , Cao W. , Lv Y.-G. , Liu Z. , other authors . ( 2012;). Recombination and natural selection in hepatitis E virus genotypes. J Med Virol 84: 1396–1407 [CrossRef] [PubMed].
    [Google Scholar]
  5. Cochrane A. , Searle B. , Hardie A. , Robertson R. , Delahooke T. , Cameron S. , Tedder R.S. , Dusheiko G.M. , De Lamballerie X. , Simmonds P. . ( 2002;). A genetic analysis of hepatitis C virus transmission between injection drug users. J Infect Dis 186: 1212–1221 [CrossRef] [PubMed].
    [Google Scholar]
  6. Corman V.M. , Drexler J.F. , Eckerle I. , Roth W.K. , Drosten C. , Eis-Hübinger A.M. . ( 2013;). Zoonotic hepatitis E virus strains in German blood donors. Vox Sang 104: 179–180 [CrossRef] [PubMed].
    [Google Scholar]
  7. Drexler J.F. , Seelen A. , Corman V.M. , Fumie Tateno A. , Cottontail V. , Melim Zerbinati R. , Gloza-Rausch F. , Klose S.M. , Adu-Sarkodie Y. , other authors . ( 2012;). Bats worldwide carry hepatitis E virus-related viruses that form a putative novel genus within the family Hepeviridae . J Virol 86: 9134–9147 [CrossRef] [PubMed].
    [Google Scholar]
  8. Fan J. . ( 2009;). Open reading frame structure analysis as a novel genotyping tool for hepatitis E virus and the subsequent discovery of an inter-genotype recombinant. J Gen Virol 90: 1353–1358 [CrossRef] [PubMed].
    [Google Scholar]
  9. Gallian P. , Lhomme S. , Piquet Y. , Sauné K. , Abravanel F. , Assal A. , Tiberghien P. , Izopet J. . ( 2014;). Hepatitis E virus infections in blood donors, France. Emerg Infect Dis 20: 1914–1917 [CrossRef] [PubMed].
    [Google Scholar]
  10. Geng Y. , Zhao C. , Song A. , Wang J. , Zhang X. , Harrison T.J. , Zhou Y. , Wang W. , Wang Y. . ( 2011;). The serological prevalence and genetic diversity of hepatitis E virus in farmed rabbits in China. Infect Genet Evol 11: 476–482 [CrossRef] [PubMed].
    [Google Scholar]
  11. Hewitt P.E. , Ijaz S. , Brailsford S.R. , Brett R. , Dicks S. , Haywood B. , Kennedy I.T.R. , Kitchen A. , Patel P. , other authors . ( 2014;). Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet 384: 1766–1773 [CrossRef] [PubMed].
    [Google Scholar]
  12. Huzly D. , Umhau M. , Bettinger D. , Cathomen T. , Emmerich F. , Hasselblatt P. , Hengel H. , Herzog R. , Kappert O. , other authors . ( 2014;). Transfusion-transmitted hepatitis E in Germany, 2013. Euro Surveill 19: 20812 [PubMed].[CrossRef]
    [Google Scholar]
  13. Ijaz S. , Vyse A.J. , Morgan D. , Pebody R.G. , Tedder R.S. , Brown D. . ( 2009;). Indigenous hepatitis E virus infection in England: more common than it seems. J Clin Virol 44: 272–276 [CrossRef] [PubMed].
    [Google Scholar]
  14. Ijaz S. , Said B. , Boxall E. , Smit E. , Morgan D. , Tedder R.S. . ( 2014;). Indigenous hepatitis E in England and wales from 2003 to 2012: evidence of an emerging novel phylotype of viruses. J Infect Dis 209: 1212–1218 [CrossRef] [PubMed].
    [Google Scholar]
  15. Inoue J. , Nishizawa T. , Takahashi M. , Aikawa T. , Mizuo H. , Suzuki K. , Shimosegawa T. , Okamoto H. . ( 2006;). Analysis of the full-length genome of genotype 4 hepatitis E virus isolates from patients with fulminant or acute self-limited hepatitis E. J Med Virol 78: 476–484 [CrossRef] [PubMed].
    [Google Scholar]
  16. Inoue J. , Takahashi M. , Mizuo H. , Suzuki K. , Aikawa T. , Shimosegawa T. , Okamoto H. . ( 2009;). Nucleotide substitutions of hepatitis E virus genomes associated with fulminant hepatitis and disease severity. Tohoku J Exp Med 218: 279–284 [CrossRef] [PubMed].
    [Google Scholar]
  17. Izopet J. , Dubois M. , Bertagnoli S. , Lhomme S. , Marchandeau S. , Boucher S. , Kamar N. , Abravanel F. , Guérin J.-L. . ( 2012;). Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France. Emerg Infect Dis 18: 1274–1281 [CrossRef] [PubMed].
    [Google Scholar]
  18. Jeblaoui A. , Haim-Boukobza S. , Marchadier E. , Mokhtari C. , Roque-Afonso A.-M. . ( 2013;). Genotype 4 hepatitis e virus in france: an autochthonous infection with a more severe presentation. Clin Infect Dis 57: e122–e126 [CrossRef] [PubMed].
    [Google Scholar]
  19. Johne R. , Reetz J. , Ulrich R.G. , Machnowska P. , Sachsenröder J. , Nickel P. , Hofmann J. . ( 2014;). An ORF1-rearranged hepatitis E virus derived from a chronically infected patient efficiently replicates in cell culture. J Viral Hepat 21: 447–456 [CrossRef] [PubMed].
    [Google Scholar]
  20. Juhl D. , Baylis S.A. , Blümel J. , Görg S. , Hennig H. . ( 2014;). Seroprevalence and incidence of hepatitis E virus infection in German blood donors. Transfusion 54: 49–56 [CrossRef] [PubMed].
    [Google Scholar]
  21. Lu L. , Li C. , Hagedorn C.H. . ( 2006;). Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol 16: 5–36 [CrossRef] [PubMed].
    [Google Scholar]
  22. Mizuo H. , Yazaki Y. , Sugawara K. , Tsuda F. , Takahashi M. , Nishizawa T. , Okamoto H. . ( 2005;). Possible risk factors for the transmission of hepatitis E virus and for the severe form of hepatitis E acquired locally in Hokkaido, Japan. J Med Virol 76: 341–349 [CrossRef] [PubMed].
    [Google Scholar]
  23. Moal V. , Gerolami R. , Colson P. . ( 2012;). First human case of co-infection with two different subtypes of hepatitis E virus. Intervirology 55: 484–487 [CrossRef] [PubMed].
    [Google Scholar]
  24. Ohnishi S. , Kang J.-H. , Maekubo H. , Arakawa T. , Karino Y. , Toyota J. , Takahashi K. , Mishiro S. . ( 2006;). Comparison of clinical features of acute hepatitis caused by hepatitis E virus (HEV) genotypes 3 and 4 in Sapporo, Japan. Hepatol Res 36: 301–307 [CrossRef] [PubMed].
    [Google Scholar]
  25. Oliveira-Filho E.F. , König M. , Thiel H.-J. . ( 2013;). Genetic variability of HEV isolates: inconsistencies of current classification. Vet Microbiol 165: 148–154 [CrossRef] [PubMed].
    [Google Scholar]
  26. Patra S. , Kumar A. , Trivedi S.S. , Puri M. , Sarin S.K. . ( 2007;). Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med 147: 28–33 [CrossRef] [PubMed].
    [Google Scholar]
  27. Pujhari S.K. , Kumar S. , Ratho R.K. , Chawla Y.K. , Chakraborti A. . ( 2010;). Phylogenetic analysis and subtyping of acute and fulminant strains of hepatitis E virus isolates of North India with reference to disease severity. Arch Virol 155: 1483–1486 [CrossRef] [PubMed].
    [Google Scholar]
  28. Ramalingam S. , Smith D. , Wellington L. , Vanek J. , Simmonds P. , MacGilchrist A. , Bathgate A. , Simpson K. , Johannessen I. . ( 2013;). Autochthonous hepatitis E in Scotland. J Clin Virol 58: 619–623 [CrossRef] [PubMed].
    [Google Scholar]
  29. Riezebos-Brilman A. , Verschuuren E.A.M. , van Son W.J. , van Imhoff G.W. , Brügemann J. , Blokzijl H. , Niesters H.G.M. . ( 2013;). The clinical course of hepatitis E virus infection in patients of a tertiary Dutch hospital over a 5-year period. J Clin Virol 58: 509–514 [CrossRef] [PubMed].
    [Google Scholar]
  30. Simmonds P. . ( 2012;). sse: a nucleotide and amino acid sequence analysis platform. BMC Res Notes 5: 50 [CrossRef] [PubMed].
    [Google Scholar]
  31. Smith D.B. , Simmonds P. . ( 2015;). Hepatitis E virus and fulminant hepatitis – a virus or host-specific pathology?. Liver Int 35: 1334–1340 [CrossRef] [PubMed].
    [Google Scholar]
  32. Smith D.B. , Purdy M.A. , Simmonds P. . ( 2013a;). Genetic variability and the classification of hepatitis E virus. J Virol 87: 4161–4169 [CrossRef] [PubMed].
    [Google Scholar]
  33. Smith D.B. , Vanek J. , Wellington L. , Johannessen I. , Ramalingam S. , Simmonds P. . ( 2013b;). Hepatitis E virus mixed infection in immunocompetent patient. Emerg Infect Dis 19: 468–470 [CrossRef] [PubMed].
    [Google Scholar]
  34. Smith D.B. , Simmonds P. , Jameel S. , Emerson S.U. , Harrison T.J. , Meng X.-J. , Okamoto H. , Van der Poel W.H.M. , Purdy M.A. . ( 2014;). Consensus proposals for classification of the family Hepeviridae . J Gen Virol 95: 2223–2232 [CrossRef] [PubMed].
    [Google Scholar]
  35. Sugawara N. , Yawata A. , Takahashi K. , Abe N. , Arai M. . ( 2009;). [The third case of fulminant hepatitis associated with ‘Kitami/Abashiri strain’ of hepatitis E virus genotype 4]. Kanzo 50: 473–474 (in Japanese with English Abstract).[CrossRef]
    [Google Scholar]
  36. Takahashi K. , Okamoto H. , Abe N. , Kawakami M. , Matsuda H. , Mochida S. , Sakugawa H. , Suginoshita Y. , Watanabe S. , other authors . ( 2009;). Virulent strain of hepatitis E virus genotype 3, Japan. Emerg Infect Dis 15: 704–709 [CrossRef] [PubMed].
    [Google Scholar]
  37. Tamura K. , Stecher G. , Peterson D. , Filipski A. , Kumar S. . ( 2013;). mega6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol 30: 2725–2729 [CrossRef] [PubMed].
    [Google Scholar]
  38. van Cuyck H. , Fan J. , Robertson D.L. , Roques P. . ( 2005;). Evidence of recombination between divergent hepatitis E viruses. J Virol 79: 9306–9314 [CrossRef] [PubMed].
    [Google Scholar]
  39. Vina-Rodriguez A. , Schlosser J. , Becher D. , Kaden V. , Groschup M.H. , Eiden M. . ( 2015;). Hepatitis E virus genotype 3 diversity: phylogenetic analysis and presence of subtype 3b in wild boar in Europe. Viruses 7: 2704–2726 [CrossRef] [PubMed].
    [Google Scholar]
  40. Vollmer T. , Diekmann J. , Johne R. , Eberhardt M. , Knabbe C. , Dreier J. . ( 2012;). Novel approach for detection of hepatitis E virus infection in German blood donors. J Clin Microbiol 50: 2708–2713 [CrossRef] [PubMed].
    [Google Scholar]
  41. Wang H. , Zhang W. , Ni B. , Shen H. , Song Y. , Wang X. , Shao S. , Hua X. , Cui L. . ( 2010;). Recombination analysis reveals a double recombination event in hepatitis E virus. Virol J 7: 129 [CrossRef] [PubMed].
    [Google Scholar]
  42. Widén F. , Sundqvist L. , Matyi-Toth A. , Metreveli G. , Belák S. , Hallgren G. , Norder H. . ( 2011;). Molecular epidemiology of hepatitis E virus in humans, pigs and wild boars in Sweden. Epidemiol Infect 139: 361–371 [CrossRef] [PubMed].
    [Google Scholar]
  43. Xia H. , Liu L. , Linde A.-M. , Belák S. , Norder H. , Widén F. . ( 2008;). Molecular characterization and phylogenetic analysis of the complete genome of a hepatitis E virus from European swine. Virus Genes 37: 39–48 [CrossRef] [PubMed].
    [Google Scholar]
  44. Zhao C. , Ma Z. , Harrison T.J. , Feng R. , Zhang C. , Qiao Z. , Fan J. , Ma H. , Li M. , other authors . ( 2009;). A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol 81: 1371–1379 [CrossRef] [PubMed].
    [Google Scholar]
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