Clin Exp Vaccine Res.  2014 Jan;3(1):29-36. 10.7774/cevr.2014.3.1.29.

Hepatitis E virus infections in humans and animals

• Song YJ
• Park WJ
• Park BJ
• Lee JB
• Park SY
• Song CS
• Lee NH
• Seo KH
• Kang YS
• Choi IS

• KMID: 2049093
• DOI: http://doi.org/10.7774/cevr.2014.3.1.29

Abstract

Hepatitis E has traditionally been considered an endemic disease of developing countries. It generally spreads through contaminated water. However, seroprevalence studies have shown that hepatitis E virus (HEV) infections are not uncommon in industrialized countries. In addition, the number of autochthonous hepatitis E cases in these countries is increasing. Most HEV infections in developed countries can be traced to the ingestion of contaminated raw or undercooked pork meat or sausages. Several animal species, including pigs, are known reservoirs of HEV that transmit the virus to humans. HEVs are now recognized as an emerging zoonotic agent. In this review, we describe the general characteristics of HEVs isolated from humans and animals, the risk factors for human HEV infection, and the current status of human vaccine development.

Keyword

Hepatitis E virus; Zoonoses; Animals; Humans; Vaccines

MeSH Terms

Animals*
Developed Countries
Developing Countries
Eating
Endemic Diseases
Hepatitis E virus*
Hepatitis E*
Hepatitis*
Humans*
Meat
Risk Factors
Seroepidemiologic Studies
Swine
Vaccines
Viruses
Water Pollution
Zoonoses
Vaccines
Water Pollution

Reference

1. Emerson SU, Purcell RH. Hepatitis E virus. In : Knipe DM, Howley PM, Griffin DE, editors. Fields virology. 5th ed. Philadelphia: Lippincott Williams & Wilkins;2006. p. 3047–3058.

2. Reyes GR, Purdy MA, Kim JP, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990; 247:1335–1339.

3. Tam AW, Smith MM, Guerra ME, et al. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology. 1991; 185:120–131.

4. Huang CC, Nguyen D, Fernandez J, et al. Molecular cloning and sequencing of the Mexico isolate of hepatitis E virus (HEV). Virology. 1992; 191:550–558.

5. Schlauder GG, Dawson GJ, Erker JC, et al. 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. 1998; 79(Pt 3):447–456.

6. Wang Y, Ling R, Erker JC, et al. A divergent genotype of hepatitis E virus in Chinese patients with acute hepatitis. J Gen Virol. 1999; 80(Pt 1):169–177.

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

8. Smith DB, Purdy MA, Simmonds P. Genetic variability and the classification of hepatitis E virus. J Virol. 2013; 87:4161–4169.

9. Arankalle VA, Chadha MS, Tsarev SA, et al. Seroepidemiology of water-borne hepatitis in India and evidence for a third enterically-transmitted hepatitis agent. Proc Natl Acad Sci U S A. 1994; 91:3428–3432.

10. Corwin AL, Khiem HB, Clayson ET, et al. A waterborne outbreak of hepatitis E virus transmission in southwestern Vietnam. Am J Trop Med Hyg. 1996; 54:559–562.

11. Clayson ET, Shrestha MP, Vaughn DW, et al. Rates of hepatitis E virus infection and disease among adolescents and adults in Kathmandu, Nepal. J Infect Dis. 1997; 176:763–766.

12. Kumar S, Subhadra S, Singh B, Panda BK. Hepatitis E virus: the current scenario. Int J Infect Dis. 2013; 17:e228–e233.

13. Gurley ES, Halder AK, Streatfield PK, et al. Estimating the burden of maternal and neonatal deaths associated with jaundice in Bangladesh: possible role of hepatitis E infection. Am J Public Health. 2012; 102:2248–2254.

14. Hamid SS, Jafri SM, Khan H, Shah H, Abbas Z, Fields H. Fulminant hepatic failure in pregnant women: acute fatty liver or acute viral hepatitis? J Hepatol. 1996; 25:20–27.

15. Rayis DA, Jumaa AM, Gasim GI, Karsany MS, Adam I. An outbreak of hepatitis E and high maternal mortality at Port Sudan, Eastern Sudan. Pathog Glob Health. 2013; 107:66–68.

16. Goumba AI, Konamna X, Komas NP. Clinical and epidemiological aspects of a hepatitis E outbreak in Bangui, Central African Republic. BMC Infect Dis. 2011; 11:93.

17. Terzic D, Dupanovic B, Mugosa B, Draskovic N, Svirtlih N. Acute hepatitis E in Montenegro: epidemiology, clinical and laboratory features. Ann Hepatol. 2009; 8:203–206.

18. Turner J, Godkin A, Neville P, Kingham J, Ch'ng CL. Clinical characteristics of hepatitis E in a "Non-Endemic" population. J Med Virol. 2010; 82:1899–1902.

19. Piper-Jenks N, Horowitz HW, Schwartz E. Risk of hepatitis E infection to travelers. J Travel Med. 2000; 7:194–199.

20. Benjelloun S, Bahbouhi B, Bouchrit N, et al. Seroepidemiological study of an acute hepatitis E outbreak in Morocco. Res Virol. 1997; 148:279–287.

21. Coursaget P, Buisson Y, Enogat N, et al. Outbreak of enterically-transmitted hepatitis due to hepatitis A and hepatitis E viruses. J Hepatol. 1998; 28:745–750.

22. Guthmann JP, Klovstad H, Boccia D, et al. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin Infect Dis. 2006; 42:1685–1691.

23. Centers for Disease Control and Prevention (CDC). Hepatitis E among U.S. travelers, 1989-1992. MMWR Morb Mortal Wkly Rep. 1993; 42:1–4.

24. Johansson PJ, Mushahwar IK, Norkrans G, Weiland O, Nordenfelt E. Hepatitis E virus infections in patients with acute hepatitis non-A-D in Sweden. Scand J Infect Dis. 1995; 27:543–546.

25. La Rosa G, Muscillo M, Vennarucci VS, Garbuglia AR, La Scala P, Capobianchi MR. Hepatitis E virus in Italy: molecular analysis of travel-related and autochthonous cases. J Gen Virol. 2011; 92:1617–1626.

26. Schlauder GG, Desai SM, Zanetti AR, Tassopoulos NC, Mushahwar IK. Novel hepatitis E virus (HEV) isolates from Europe: evidence for additional genotypes of HEV. J Med Virol. 1999; 57:243–251.

27. Thomas DL, Yarbough PO, Vlahov D, et al. Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J Clin Microbiol. 1997; 35:1244–1247.

28. Xu C, Wang RY, Schechterly CA, et al. An assessment of hepatitis E virus (HEV) in US blood donors and recipients: no detectable HEV RNA in 1939 donors tested and no evidence for HEV transmission to 362 prospectively followed recipients. Transfusion. 2013; 53(10 Pt 2):2505–2511.

29. Faber MS, Wenzel JJ, Jilg W, Thamm M, Hohle M, Stark K. Hepatitis E virus seroprevalence among adults, Germany. Emerg Infect Dis. 2012; 18:1654–1657.

30. Ijaz S, Vyse AJ, Morgan D, Pebody RG, Tedder RS, Brown D. Indigenous hepatitis E virus infection in England: more common than it seems. J Clin Virol. 2009; 44:272–276.

31. Mansuy JM, Bendall R, Legrand-Abravanel F, et al. Hepatitis E virus antibodies in blood donors, France. Emerg Infect Dis. 2011; 17:2309–2312.

32. Romano L, Paladini S, Tagliacarne C, Canuti M, Bianchi S, Zanetti AR. Hepatitis E in Italy: a long-term prospective study. J Hepatol. 2011; 54:34–40.

33. Chiu DM, Chan MC, Yeung AC, Ngai KL, Chan PK. Seroprevalence of hepatitis E virus in Hong Kong, 2008-2009. J Med Virol. 2013; 85:459–461.

34. Dong C, Dai X, Shao JS, Hu K, Meng JH. Identification of genetic diversity of hepatitis E virus (HEV) and determination of the seroprevalence of HEV in eastern China. Arch Virol. 2007; 152:739–746.

35. Lee JT, Shao PL, Chang LY, et al. Seroprevalence of hepatitis E virus infection among swine farmers and the general population in rural Taiwan. PLoS One. 2013; 8:e67180.

36. Li RC, Ge SX, Li YP, et al. Seroprevalence of hepatitis E virus infection, rural southern People's Republic of China. Emerg Infect Dis. 2006; 12:1682–1688.

37. Taniguchi M, Kim SR, Mishiro S, et al. Epidemiology of hepatitis E in Northeastern China, South Korea and Japan. J Infect. 2009; 58:232–237.

38. Krumbholz A, Mohn U, Lange J, et al. Prevalence of hepatitis E virus-specific antibodies in humans with occupational exposure to pigs. Med Microbiol Immunol. 2012; 201:239–244.

39. Meng XJ, Wiseman B, Elvinger F, et al. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol. 2002; 40:117–122.

40. Olsen B, Axelsson-Olsson D, Thelin A, Weiland O. Unexpected high prevalence of IgG-antibodies to hepatitis E virus in Swedish pig farmers and controls. Scand J Infect Dis. 2006; 38:55–58.

41. Galiana C, Fernandez-Barredo S, Garcia A, Gomez MT, Perez-Gracia MT. Occupational exposure to hepatitis E virus (HEV) in swine workers. Am J Trop Med Hyg. 2008; 78:1012–1015.

42. Clayson ET, Innis BL, Myint KS, et al. Detection of hepatitis E virus infections among domestic swine in the Kathmandu Valley of Nepal. Am J Trop Med Hyg. 1995; 53:228–232.

43. Meng XJ, Purcell RH, Halbur PG, et al. A novel virus in swine is closely related to the human hepatitis E virus. Proc Natl Acad Sci U S A. 1997; 94:9860–9865.

44. Chandler JD, Riddell MA, Li F, Love RJ, Anderson DA. Serological evidence for swine hepatitis E virus infection in Australian pig herds. Vet Microbiol. 1999; 68:95–105.

45. Meng XJ, Dea S, Engle RE, et al. Prevalence of antibodies to the hepatitis E virus in pigs from countries where hepatitis E is common or is rare in the human population. J Med Virol. 1999; 59:297–302.

46. Choi IS, Kwon HJ, Shin NR, Yoo HS. Identification of swine hepatitis E virus (HEV) and prevalence of anti-HEV antibodies in swine and human populations in Korea. J Clin Microbiol. 2003; 41:3602–3608.

47. Kim SE, Kim MY, Kim DG, et al. Determination of fecal shedding rates and genotypes of swine hepatitis E virus (HEV) in Korea. J Vet Med Sci. 2008; 70:1367–1371.

48. Huang FF, Haqshenas G, Guenette DK, et al. Detection by reverse transcription-PCR and genetic characterization of field isolates of swine hepatitis E virus from pigs in different geographic regions of the United States. J Clin Microbiol. 2002; 40:1326–1332.

49. Takahashi M, Nishizawa T, Miyajima H, et al. Swine hepatitis E virus strains in Japan form four phylogenetic clusters comparable with those of Japanese isolates of human hepatitis E virus. J Gen Virol. 2003; 84(Pt 4):851–862.

50. Meng XJ, Halbur PG, Shapiro MS, et al. Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J Virol. 1998; 72:9714–9721.

51. Arankalle VA, Chobe LP, Chadha MS. Type-IV Indian swine HEV infects rhesus monkeys. J Viral Hepat. 2006; 13:742–745.

52. Feagins AR, Opriessnig T, Huang YW, Halbur PG, Meng XJ. Cross-species infection of specific-pathogen-free pigs by a genotype 4 strain of human hepatitis E virus. J Med Virol. 2008; 80:1379–1386.

53. Feagins AR, Cordoba L, Sanford BJ, et al. Intergenotypic chimeric hepatitis E viruses (HEVs) with the genotype 4 human HEV capsid gene in the backbone of genotype 3 swine HEV are infectious in pigs. Virus Res. 2011; 156:141–146.

54. Sato Y, Sato H, Naka K, et al. 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. 2011; 156:1345–1358.

55. Haqshenas G, Huang FF, Fenaux M, et al. The putative capsid protein of the newly identified avian hepatitis E virus shares antigenic epitopes with that of swine and human hepatitis E viruses and chicken big liver and spleen disease virus. J Gen Virol. 2002; 83(Pt 9):2201–2209.

56. Huang FF, Haqshenas G, Shivaprasad HL, et al. Heterogeneity and seroprevalence of a newly identified avian hepatitis E virus from chickens in the United States. J Clin Microbiol. 2002; 40:4197–4202.

57. Kwon HM, Sung HW, Meng XJ. Serological prevalence, genetic identification, and characterization of the first strains of avian hepatitis E virus from chickens in Korea. Virus Genes. 2012; 45:237–245.

58. Huang FF, Sun ZF, Emerson SU, et al. Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV. J Gen Virol. 2004; 85(Pt 6):1609–1618.

59. Bilic I, Jaskulska B, Basic A, Morrow CJ, Hess M. Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes. J Gen Virol. 2009; 90(Pt 4):863–873.

60. Marek A, Bilic I, Prokofieva I, Hess M. Phylogenetic analysis of avian hepatitis E virus samples from European and Australian chicken flocks supports the existence of a different genus within the Hepeviridae comprising at least three different genotypes. Vet Microbiol. 2010; 145:54–61.

61. Guo H, Zhou EM, Sun ZF, Meng XJ, Halbur PG. Identification of B-cell epitopes in the capsid protein of avian hepatitis E virus (avian HEV) that are common to human and swine HEVs or unique to avian HEV. J Gen Virol. 2006; 87(Pt 1):217–223.

62. Zhao C, Ma Z, Harrison TJ, et al. A novel genotype of hepatitis E virus prevalent among farmed rabbits in China. J Med Virol. 2009; 81:1371–1379.

63. Cossaboom CM, Cordoba L, Cao D, Ni YY, Meng XJ. Complete genome sequence of hepatitis E virus from rabbits in the United States. J Virol. 2012; 86:13124–13125.

64. Cossaboom CM, Cordoba L, Sanford BJ, et al. 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. 2012; 93(Pt 8):1687–1695.

65. Lhomme S, Dubois M, Abravanel F, et al. Risk of zoonotic transmission of HEV from rabbits. J Clin Virol. 2013; 58:357–362.

66. Kabrane-Lazizi Y, Fine JB, Elm J, et al. Evidence for widespread infection of wild rats with hepatitis E virus in the United States. Am J Trop Med Hyg. 1999; 61:331–335.

67. Johne R, Plenge-Bonig A, Hess M, Ulrich RG, Reetz J, Schielke A. Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J Gen Virol. 2010; 91(Pt 3):750–758.

68. Lack JB, Volk K, Van Den Bussche RA. Hepatitis E virus genotype 3 in wild rats, United States. Emerg Infect Dis. 2012; 18:1268–1273.

69. Kanai Y, Miyasaka S, Uyama S, et al. Hepatitis E virus in Norway rats (Rattus norvegicus) captured around a pig farm. BMC Res Notes. 2012; 5:4.

70. Li TC, Ami Y, Suzaki Y, et al. Characterization of full genome of rat hepatitis E virus strain from Vietnam. Emerg Infect Dis. 2013; 19:115–118.

71. Mulyanto , Depamede SN, Sriasih M, et al. Frequent detection and characterization of hepatitis E virus variants in wild rats (Rattus rattus) in Indonesia. Arch Virol. 2013; 158:87–96.

72. Li TC, Yoshizaki S, Ami Y, et al. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses. Vet Microbiol. 2013; 163:54–61.

73. Purcell RH, Engle RE, Rood MP, et al. Hepatitis E virus in rats, Los Angeles, California, USA. Emerg Infect Dis. 2011; 17:2216–2222.

74. Drexler JF, Seelen A, Corman VM, et al. Bats worldwide carry hepatitis E virus-related viruses that form a putative novel genus within the family Hepeviridae. J Virol. 2012; 86:9134–9147.

75. Raj VS, Smits SL, Pas SD, et al. Novel hepatitis E virus in ferrets, the Netherlands. Emerg Infect Dis. 2012; 18:1369–1370.

76. Sanford BJ, Emerson SU, Purcell RH, et al. Serological evidence for a hepatitis E virus-related agent in goats in the United States. Transbound Emerg Dis. 2012; 08. 22. doi: 10.1111/tbed.12001. [Epub ahead of print].

77. Masuda J, Yano K, Tamada Y, et al. Acute hepatitis E of a man who consumed wild boar meat prior to the onset of illness in Nagasaki, Japan. Hepatol Res. 2005; 31:178–183.

78. Miyashita K, Kang JH, Saga A, et al. Three cases of acute or fulminant hepatitis E caused by ingestion of pork meat and entrails in Hokkaido, Japan: Zoonotic food-borne transmission of hepatitis E virus and public health concerns. Hepatol Res. 2012; 42:870–878.

79. Tei S, Kitajima N, Ohara S, et al. Consumption of uncooked deer meat as a risk factor for hepatitis E virus infection: an age- and sex-matched case-control study. J Med Virol. 2004; 74:67–70.

80. Takahashi K, Kitajima N, Abe N, Mishiro S. 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. 2004; 330:501–505.

81. Colson P, Borentain P, Queyriaux B, et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis. 2010; 202:825–834.

82. Berto A, Grierson S, Hakze-van der Honing R, et al. Hepatitis E virus in pork liver sausage, France. Emerg Infect Dis. 2013; 19:264–266.

83. Bouwknegt M, Rutjes SA, Reusken CB, et al. The course of hepatitis E virus infection in pigs after contact-infection and intravenous inoculation. BMC Vet Res. 2009; 5:7.

84. Kim YM, Jeong SH, Kim JY, et al. The first case of genotype 4 hepatitis E related to wild boar in South Korea. J Clin Virol. 2011; 50:253–256.

85. Song YJ, Jeong HJ, Kim YJ, et al. Analysis of complete genome sequences of swine hepatitis E virus and possible risk factors for transmission of HEV to humans in Korea. J Med Virol. 2010; 82:583–591.

86. Balayan MS. Hepatitis E virus infection in Europe: regional situation regarding laboratory diagnosis and epidemiology. Clin Diagn Virol. 1993; 1:1–9.

87. Meng J, Dai X, Chang JC, et al. Identification and characterization of the neutralization epitope(s) of the hepatitis E virus. Virology. 2001; 288:203–211.

88. Schofield DJ, Glamann J, Emerson SU, Purcell RH. Identification by phage display and characterization of two neutralizing chimpanzee monoclonal antibodies to the hepatitis E virus capsid protein. J Virol. 2000; 74:5548–5555.

89. Zhang H, Dai X, Shan X, Meng J. Characterization of antigenic epitopes of the ORF2 protein from hepatitis E virus genotype 4. Virus Res. 2009; 142:140–143.

90. Jiménez de Oya N, Escribano-Romero E, Blazquez AB, et al. Characterization of hepatitis E virus recombinant ORF2 proteins expressed by vaccinia viruses. J Virol. 2012; 86:7880–7886.

91. Kamili S, Spelbring J, Carson D, Krawczynski K. Protective efficacy of hepatitis E virus DNA vaccine administered by gene gun in the cynomolgus macaque model of infection. J Infect Dis. 2004; 189:258–264.

92. Li SW, Zhang J, Li YM, et al. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine. 2005; 23:2893–2901.

93. Wu T, Li SW, Zhang J, Ng MH, Xia NS, Zhao Q. Hepatitis E vaccine development: a 14 year odyssey. Hum Vaccin Immunother. 2012; 8:823–827.

94. Zhang J, Shih JW, Wu T, Li SW, Xia NS. Development of the hepatitis E vaccine: from bench to field. Semin Liver Dis. 2013; 33:79–88.

95. Zhu FC, Zhang J, Zhang XF, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010; 376:895–902.