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Hepatitis E Virus

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Hepatitis E Virus

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 948))

Abstract

Since the sequence of hepatitis E virus (HEV) was determined from a patient with enterically transmitted non-A, non-B hepatitis in 1989, similar sequences have been isolated from many different animals, including pigs, wild boars, deer, rabbits, bats, rats, chicken, and trout. All of these sequences have the same genomic organization, which contains open reading frames (ORFs) 1, 2, and 3, although their genomic sequences are variable. Some have proposed that they be classified as new family, Hepeviridae, which would be further divided into different genera and species according to their sequence variability. The size of these virus particles generally ranged from 27 to 34 nm. However, HEV virions produced in cell culture differ in structure from the viruses found in feces. Those from cell culture have a lipid envelope and a little ORF3 on their surfaces, whereas the viruses isolated from feces lack lipid envelope and ORF3. Surprisingly, most of the secreted ORF2 protein from both these sources is not associated with HEV RNA.

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Abbreviations

ET-NANBH:

Enterically transmitted non-A, non-B hepatitis

HAV:

Hepatitis A virus

HBV:

Hepatitis B virus

Hel:

RNA helicase

HEV:

Hepatitis E virus

MeT:

Methyltransferase

NTR:

Non-translating region

ORF:

Open reading frame

PCP:

Papain-like cysteine protease

RdRp:

RNA-dependent RNA polymerase

SISPA:

Sequence-independent single-primer amplification

UTR:

Untranslated region

References

  1. Balayan MS, Andjaparidze AG, Savinskaya SS, Ketiladze ES, Braginsky DM, Savinov AP, Poleschuk VF (1983) Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology 20:23–31

    Article  CAS  PubMed  Google Scholar 

  2. Batts W, Yun S, Hedrick R, Winton J (2011) A novel member of the family Hepeviridae from cutthroat trout (Oncorhynchus clarkii). Virus Res 158:116–123

    Article  CAS  PubMed  Google Scholar 

  3. Bi SL, Purdy MA, McCaustland KA, Margolis HS, Bradley DW (1993) The sequence of hepatitis E virus isolated directly from a single source during an outbreak in China. Virus Res 28:233–247

    Article  CAS  PubMed  Google Scholar 

  4. Bradley DW, Krawczynski K, Cook EH Jr, McCaustland KA, Humphrey CD, Spelbring JE, Myint H, Maynard JE (1987) Enterically transmitted non-A, non-B hepatitis: serial passage of disease in cynomolgus macaques and tamarins and recovery of disease-associated 27- to 34-nm virus-like particles. Proc Natl Acad Sci U S A 84:6277–6281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bradley DW, Purdy MA, Reyes GR (1991) Hepatitis E virus genome. Molecular features, expression of immunoreactive proteins and sequence divergence. J Hepatol 13(Suppl 4):S152–S154

    Article  CAS  PubMed  Google Scholar 

  6. Buisson Y, Grandadam M, Nicand E, Cheval P, van Cuyck-Gandre H, Innis B, Rehel P, Coursaget P, Teyssou R, Tsarev S (2000) Identification of a novel hepatitis E virus in Nigeria. J Gen Virol 81:903–909

    Article  CAS  PubMed  Google Scholar 

  7. Centers for Disease Control (1987) Enterically transmitted non-A, non-B hepatitis—Mexico. MMWR Morb Mortal Wkly Rep 36:597–602

    Google Scholar 

  8. Chatterjee R, Tsarev S, Pillot J, Coursaget P, Emerson SU, Purcell RH (1997) African strains of hepatitis E virus that are distinct from Asian strains. J Med Virol 53:139–144

    Article  CAS  PubMed  Google Scholar 

  9. Cossaboom CM, Cordoba L, Sanford BJ, Pineyro P, Kenney SP, Dryman BA, Wang Y, Meng XJ (2012) Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States. J Gen Virol 93:1687–1695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. De Cock KM, Bradley DW, Sandford NL, Govindarajan S, Maynard JE, Redeker AG (1987) Epidemic non-A, non-B hepatitis in patients from Pakistan. Ann Intern Med 106:227–230

    Article  PubMed  Google Scholar 

  11. Drexler JF, Seelen A, Corman VM, Fumie Tateno A, Cottontail V, Melim Zerbinati R, Gloza-Rausch F, Klose SM, Adu-Sarkodie Y, Oppong SK, Kalko EK, Osterman A, Rasche A, Adam A, Muller MA, Ulrich RG, Leroy EM, Lukashev AN, Drosten C (2012) Bats worldwide carry hepatitis E virus-related viruses that form a putative novel genus within the family Hepeviridae. J Virol 86:9134–9147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Emerson S, Anderson D, Arankalle A, Meng X, Purdy M, Schlauder G, Tsarev S (2004) Hepevirus. In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA (eds) Virus taxonomy, VIIIth report of the ICTV. Elsevier/Academic Press, London, pp 851–855

    Google Scholar 

  13. Geng Y, Zhang H, Li J, Huang W, Harrison TJ, Zhao C, Zhou Y, Lian H, Wang Y (2013) Comparison of hepatitis E virus genotypes from rabbits and pigs in the same geographic area: no evidence of natural cross-species transmission between the two animals. Infect Genet Evol 13:304–309

    Article  PubMed  Google Scholar 

  14. Geng Y, Zhao C, Song A, Wang J, Zhang X, Harrison TJ, 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

    Article  PubMed  Google Scholar 

  15. Gouvea V, Snellings N, Popek MJ, Longer CF, Innis BL (1998) Hepatitis E virus: complete genome sequence and phylogenetic analysis of a Nepali isolate. Virus Res 57:21–26

    Article  CAS  PubMed  Google Scholar 

  16. Graff J, Torian U, Nguyen H, Emerson SU (2006) A bicistronic subgenomic mRNA encodes both the ORF2 and ORF3 proteins of hepatitis E virus. J Virol 80:5919–5926

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Green KY, Ando T, Balayan MS, Berke T, Clarke IN, Estes MK, Matson DO, Nakata S, Neill JD, Studdert MJ, Thiel HJ (2000) Taxonomy of the caliciviruses. J Infect Dis 181(Suppl 2):S322–S330

    Article  PubMed  Google Scholar 

  18. Haqshenas G, Shivaprasad HL, Woolcock PR, Read DH, Meng XJ (2001) Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. J Gen Virol 82:2449–2462

    Article  CAS  PubMed  Google Scholar 

  19. Hla M, Myint Myint S, Tun K, Thein-Maung M, Khin Maung T (1985) A clinical and epidemiological study of an epidemic of non-A non-B hepatitis in Rangoon. AmJTrop Med Hyg 34:1183–1189

    Google Scholar 

  20. Huang CC, Nguyen D, Fernandez J, Yun KY, Fry KE, Bradley DW, Tam AW, Reyes GR (1992) Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). Virology 191:550–558

    Article  CAS  PubMed  Google Scholar 

  21. Huang YW, Opriessnig T, Halbur PG, Meng XJ (2007) Initiation at the third in-frame AUG codon of open reading frame 3 of the hepatitis E virus is essential for viral infectivity in vivo. J Virol 81:3018–3026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hussaini SH, Skidmore SJ, Richardson P, Sherratt LM, Cooper BT, O’Grady JG (1997) Severe hepatitis E infection during pregnancy. J Viral Hepat 4:51–54

    Article  CAS  PubMed  Google Scholar 

  23. Izopet J, Dubois M, Bertagnoli S, Lhomme S, Marchandeau S, Boucher S, Kamar N, Abravanel F, Guerin JL (2012) Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France. Emerg Infect Dis 18:1274–1281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Johne R, Plenge-Bonig A, Hess M, Ulrich RG, Reetz J, Schielke A (2010) Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J Gen Virol 91:750–758

    Article  CAS  PubMed  Google Scholar 

  25. Kane MA, Bradley DW, Shrestha SM, Maynard JE, Cook EH, Mishra RP, Joshi DD (1984) Epidemic non-A, non-B hepatitis in Nepal. Recovery of a possible etiologic agent and transmission studies in marmosets. JAMA 252:3140–3145

    Article  CAS  PubMed  Google Scholar 

  26. Khuroo MS (1980) Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Am J Med 68:818–824

    Article  CAS  PubMed  Google Scholar 

  27. Koonin EV, Gorbalenya AE, Purdy MA, Rozanov MN, Reyes GR, Bradley DW (1992) 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. Proc Natl Acad Sci U S A 89:8259–8263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Lu L, Li C, Hagedorn CH (2006) Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol 16:5–36

    Article  CAS  PubMed  Google Scholar 

  29. Ma H, Geng Y, Li Z, Harrison TJ, Huang W, Zhao C, Wang Y (2013) Analysis of the complete genome sequences of one swine and two human hepatitis E virus genotype 4 strains isolated in Beijing, China. Infect Genet Evol 18:42–47

    Article  CAS  PubMed  Google Scholar 

  30. Ma H, Zheng L, Liu Y, Zhao C, Harrison TJ, Ma Y, Sun S, Zhang J, Wang Y (2010) Experimental infection of rabbits with rabbit and genotypes 1 and 4 hepatitis E viruses. PLoS One 5:e9160

    Article  PubMed  PubMed Central  Google Scholar 

  31. Meng J, Cong M, Dai X, Pillot J, Purdy MA, Fields HA, Khudyakov YE (1999) Primary structure of open reading frame 2 and 3 of the hepatitis E virus isolated from Morocco. J Med Virol 57:126–133

    Article  CAS  PubMed  Google Scholar 

  32. Meng XJ (2010) Hepatitis E virus: animal reservoirs and zoonotic risk. Vet Microbiol 140:256–265

    Article  CAS  PubMed  Google Scholar 

  33. Meng XJ, Purcell RH, Halbur PG, Lehman JR, Webb DM, Tsareva TS, Haynes JS, Thacker BJ, Emerson SU (1997) A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci U S A 94:9860–9865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pavio N, Meng XJ, Renou C (2010) Zoonotic hepatitis E: animal reservoirs and emerging risks. Vet Res 41:46

    Article  PubMed  PubMed Central  Google Scholar 

  35. Payne CJ, Ellis TM, Plant SL, Gregory AR, Wilcox GE (1999) Sequence data suggests big liver and spleen disease virus (BLSV) is genetically related to hepatitis E virus. Vet Microbiol 68:119–125

    Article  CAS  PubMed  Google Scholar 

  36. Qi Y, Zhang F, Zhang L, Harrison TJ, Huang W, Zhao C, Kong W, Jiang C, Wang Y (2015) Hepatitis E virus produced from cell culture Has a lipid envelope. PLoS One 10:e0132503

    Article  PubMed  PubMed Central  Google Scholar 

  37. Reyes GR (1993) Hepatitis E virus (HEV): molecular biology and emerging epidemiology. Prog Liver Dis 11:203–213

    CAS  PubMed  Google Scholar 

  38. Reyes GR, Huang CC, Tam AW, Purdy MA (1993) Molecular organization and replication of hepatitis E virus (HEV). Arch Virol Suppl 7:15–25

    Article  CAS  PubMed  Google Scholar 

  39. Reyes GR, Purdy MA, Kim JP, Luk KC, Young LM, Fry KE, Bradley DW (1990) Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science 247:1335–1339

    Article  CAS  PubMed  Google Scholar 

  40. Reyes GR, Yarbough PO, Tam AW, Purdy MA, Huang CC, Kim JS, Bradley DW, Fry KE (1991) Hepatitis E virus (HEV): the novel agent responsible for enterically transmitted non-A, non-B hepatitis. Gastroenterol Jpn 26(Suppl 3):142–147

    PubMed  Google Scholar 

  41. Sato Y, Sato H, Naka K, Furuya S, Tsukiji H, Kitagawa K, Sonoda Y, Usui T, Sakamoto H, Yoshino S, Shimizu Y, Takahashi M, Nagashima S, Jirintai X, Nishizawa T, Okamoto H (2011) A nationwide survey of hepatitis E virus (HEV) infection in wild boars in Japan: identification of boar HEV strains of genotypes 3 and 4 and unrecognized genotypes. Arch Virol 156:1345–1358

    Article  CAS  PubMed  Google Scholar 

  42. Schlauder GG, Dawson GJ, Erker JC, Kwo PY, Knigge MF, Smalley DL, Rosenblatt JE, Desai SM, Mushahwar IK (1998) The sequence and phylogenetic analysis of a novel hepatitis E virus isolated from a patient with acute hepatitis reported in the United States. J Gen Virol 79(Pt 3):447–456

    Article  CAS  PubMed  Google Scholar 

  43. Smith DB, Simmonds P, International Committee on Taxonomy of Viruses Hepeviridae Study, G, Jameel S, Emerson SU, Harrison TJ, Meng XJ, Okamoto H, Van der Poel WH, Purdy MA (2014) Consensus proposals for classification of the family Hepeviridae. J Gen Virol 95:2223–2232

    Article  PubMed  PubMed Central  Google Scholar 

  44. Takahashi K, Kitajima N, Abe N, Mishiro S (2004) Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer. Virology 330:501–505

    Article  CAS  PubMed  Google Scholar 

  45. Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE, Reyes GR (1991) Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology 185:120–131

    Article  CAS  PubMed  Google Scholar 

  46. Tsarev SA, Binn LN, Gomatos PJ, Arthur RR, Monier MK, van Cuyck-Gandre H, Longer CF, Innis BL (1999) Phylogenetic analysis of hepatitis E virus isolates from Egypt. J Med Virol 57:68–74

    Article  CAS  PubMed  Google Scholar 

  47. Tsarev SA, Emerson SU, Reyes GR, Tsareva TS, Legters LJ, Malik IA, Iqbal M, Purcell RH (1992) Characterization of a prototype strain of hepatitis E virus. Proc Natl Acad Sci U S A 89:559–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. van Cuyck-Gandre H, Zhang HY, Tsarev SA, Clements NJ, Cohen SJ, Caudill JD, Buisson Y, Coursaget P, Warren RL, Longer CF (1997) Characterization of hepatitis E virus (HEV) from Algeria and Chad by partial genome sequence. J Med Virol 53:340–347

    Article  PubMed  Google Scholar 

  49. Viswanathan R, Sidhu AS (1957) Infectious hepatitis; clinical findings. Indian J Med Res 45:49–58

    CAS  PubMed  Google Scholar 

  50. Wang Y, Ling R, Erker JC, Zhang H, Li H, Desai S, Mushahwar IK, Harrison TJ (1999) A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. J Gen Virol 80(Pt 1):169–177

    Article  CAS  PubMed  Google Scholar 

  51. Wang Y, Zhang H, Ling R, Li H, Harrison TJ (2000) The complete sequence of hepatitis E virus genotype 4 reveals an alternative strategy for translation of open reading frames 2 and 3. J Gen Virol 81:1675–1686

    Article  CAS  PubMed  Google Scholar 

  52. Wong DC, Purcell RH, Sreenivasan MA, Prasad SR, Pavri KM (1980) Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology. Lancet 2:876–879

    Article  CAS  PubMed  Google Scholar 

  53. Woo PC, Lau SK, Teng JL, Tsang AK, Joseph M, Wong EY, Tang Y, Sivakumar S, Xie J, Bai R, Wernery R, Wernery U, Yuen KY (2014) New hepatitis E virus genotype in camels, the Middle East. Emerg Infect Dis 20:1044–1048

    Article  PubMed  PubMed Central  Google Scholar 

  54. Xi JN, Graham DY, Wang KN, Estes MK (1990) Norwalk virus genome cloning and characterization. Science 250:1580–1583

    Article  CAS  PubMed  Google Scholar 

  55. Yugo DM, Meng XJ (2013) Hepatitis E virus: foodborne, waterborne and zoonotic transmission. Int J Environ Res Public Health 10:4507–4533

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zafrullah M, Ozdener MH, Panda SK, Jameel S (1997) The ORF3 protein of hepatitis E virus is a phosphoprotein that associates with the cytoskeleton. J Virol 71:9045–9053

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Zhao C, Ma Z, Harrison TJ, Feng R, Zhang C, Qiao Z, Fan J, Ma H, Li M, Song A, Wang Y (2009) A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol 81:1371–1379

    Article  CAS  PubMed  Google Scholar 

  58. Zhuang H (1991) Advances in the research on non-A, non-B hepatitis in China. Zhonghua liu xing bing xue za zhii 12:377–379

    CAS  Google Scholar 

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Authors and Affiliations

  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, No. 2 Tiantanxili, Dongcheng District, Beijing, 100050, China

    Youchun Wang M.D., Ph.D., Chenyan Zhao Ph.D. & Ying Qi Ph.D.

  2. School of Public Health, Hebei University, No. 342 Yuhuadonglu, Baoding, 071000, China

    Yansheng Geng Ph.D.

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  1. Youchun Wang M.D., Ph.D.
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  2. Chenyan Zhao Ph.D.
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  3. Ying Qi Ph.D.
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  4. Yansheng Geng Ph.D.
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Correspondence to Youchun Wang M.D., Ph.D. .

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  1. Division of HIV/AIDS and Sex-transmitted Virus Vaccines, National Institutes for Food and Drug Control, Beijing, China

    Youchun Wang

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Wang, Y., Zhao, C., Qi, Y., Geng, Y. (2016). Hepatitis E Virus. In: Wang, Y. (eds) Hepatitis E Virus. Advances in Experimental Medicine and Biology, vol 948. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0942-0_1

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