Hepatitis E causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Taxonomy

Viruses; ssRNA viruses; ssRNA positive-strand viruses; Hepeviridae; Hepevirus; Hepatitis E virus[1]

Biology

Hepatitis E virus Centers for Disease Control and Prevention[2]

The viral particles are 27 to 34 nanometers in diameter, are nonenveloped, and contain a single-strand of positive-sense RNA that is approximately 7200 bases in length, polyadenylated at the 3' terminus, and capped at the 5'terminus.[3][4][5]

The genome of HEV contains 3 Open Reading Frames:

Genotypes

In order to study the biology of the virus and develop new treatment drugs, HEV must be grown in culture systems, such as:

  • PLC/PRF/5 cell line of hepatic carcinoma, A549 cell line of lung carcinoma, and fecal samples from an infected patient[13]
  • HepG2/C3A cell line of hepatoma[14]

Molecular studies of HEV lead to the classification of the virus into 4 genotypes:[3][15][16][17][18][6][19][20][21]

Genotypes
Genotype Characteristics
HEV1
  • Restricted to humans
  • Responsible for epidemic hepatitis
  • Water-borne disease in developing countries
  • Fecal-oral route of transmission
  • Predominant in Asia (endemic and epidemic)
  • Classified in 4 subgenotypes
HEV2
  • Restricted to humans
  • Responsible for epidemic hepatitis
  • Water-borne disease in developing countries
  • Fecal-oral route of transmission
  • Predominant in Central America and Africa
  • Classified in 2 subgenotypes
HEV3
  • Infects humans (accidental host) and other mammalian species, such as pigs, deer, shellfish and rodents (zoonosis)
  • Responsible for autochthonous hepatitis E in developed and developing countries
  • Worldwide distribution
  • Consumption of undercooked pork
  • Classified in 3 subgenotypes
  • Important zoonotic transmission
HEV4
  • Infects humans (accidental host) and other mammalian species, such as pigs (zoonosis)
  • Responsible for autochthonous hepatitis E in developed and developing countries
  • Most frequent in southeast Asia
  • Consumption of undercooked pork
  • Classified in 7 subgenotypes
HEV5
  • Recently identified in birds (Avian HEV)

Despite the epidemiological and clinical distinctions, the different genotypes are thought to belong to one same serotype, due to cross-neutralization.[22] Evidence shows that HEV has evolved and adapted to a serious of hosts, until finally being able to infect humans. HEV subgenotypes in humans and pigs have been associated, suggesting zoonotic transmission.[3][23][24]

Life Cycle

The cellular receptor for HEV and the mode of entry of the virus into the host cell are yet to be identified.[9]

The hepatitis E virus replicates in the cytoplasm of the host cell. The genomic RNA serves as template chain for replication and encodes nonstructural proteins, while subgenomic RNA produces capsid proteins.[7]

Tropism

Natural Reservoir

The natural reservoir of HEV is yet to be identified. Different observations have suggested different reservoirs:

  • Prolonged fecal shedding from patients with history of the disease has been suggested. However, the duration of viral shedding in feces is not compatible with this hypothesis.[25]
  • Environmental reservoir was suggested following detection of HEV in sewages.[26]
  • Continuous fecal shedding from asymptomatic patients was suggested as a form of maintenance of the virus, contaminating water supplies.[27]
  • The existence of an animal reservoir is supported by the detection of anti-HEV antibodies in different species.[27]

References

  1. ↑ "Hepatitis E virus taxonomy".
  2. ↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
  3. ↑ 3.0 3.1 3.2 3.3 Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J; et al. (2012). "Hepatitis E." Lancet. 379 (9835): 2477–88. doi:10.1016/S0140-6736(11)61849-7. PMID 22549046.
  4. ↑ Reyes GR, Purdy MA, Kim JP, Luk KC, Young LM, Fry KE; et al. (1990). "Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis". Science. 247 (4948): 1335–9. PMID 2107574.
  5. ↑ Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE; et al. (1991). "Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome". Virology. 185 (1): 120–31. PMID 1926770.
  6. ↑ 6.0 6.1 Wedemeyer H, Pischke S, Manns MP (2012). "Pathogenesis and treatment of hepatitis e virus infection". Gastroenterology. 142 (6): 1388–1397.e1. doi:10.1053/j.gastro.2012.02.014. PMID 22537448.
  7. ↑ 7.0 7.1 Hoofnagle JH, Nelson KE, Purcell RH (2012). "Hepatitis E." N Engl J Med. 367 (13): 1237–44. doi:10.1056/NEJMra1204512. PMID 23013075.
  8. ↑ Li TC, Yamakawa Y, Suzuki K, Tatsumi M, Razak MA, Uchida T; et al. (1997). "Expression and self-assembly of empty virus-like particles of hepatitis E virus". J Virol. 71 (10): 7207–13. PMC 192060. PMID 9311793.
  9. ↑ 9.0 9.1 Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S (2009). "Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection". J Virol. 83 (24): 12714–24. doi:10.1128/JVI.00717-09. PMC 2786843. PMID 19812150.
  10. ↑ Xing L, Wang JC, Li TC, Yasutomi Y, Lara J, Khudyakov Y; et al. (2011). "Spatial configuration of hepatitis E virus antigenic domain". J Virol. 85 (2): 1117–24. doi:10.1128/JVI.00657-10. PMC 3020005. PMID 21068233.
  11. ↑ Yamada K, Takahashi M, Hoshino Y, Takahashi H, Ichiyama K, Nagashima S; et al. (2009). "ORF3 protein of hepatitis E virus is essential for virion release from infected cells". J Gen Virol. 90 (Pt 8): 1880–91. doi:10.1099/vir.0.010561-0. PMID 19339479.
  12. ↑ Emerson SU, Nguyen HT, Torian U, Burke D, Engle R, Purcell RH (2010). "Release of genotype 1 hepatitis E virus from cultured hepatoma and polarized intestinal cells depends on open reading frame 3 protein and requires an intact PXXP motif". J Virol. 84 (18): 9059–69. doi:10.1128/JVI.00593-10. PMC 2937629. PMID 20610720.
  13. ↑ Tanaka T, Takahashi M, Kusano E, Okamoto H (2007). "Development and evaluation of an efficient cell-culture system for Hepatitis E virus". J Gen Virol. 88 (Pt 3): 903–11. doi:10.1099/vir.0.82535-0. PMID 17325363.
  14. ↑ Shukla P, Nguyen HT, Torian U, Engle RE, Faulk K, Dalton HR; et al. (2011). "Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant". Proc Natl Acad Sci U S A. 108 (6): 2438–43. doi:10.1073/pnas.1018878108. PMC 3038723. PMID 21262830.
  15. ↑ Dalton HR, Bendall R, Ijaz S, Banks M (2008). "Hepatitis E: an emerging infection in developed countries". Lancet Infect Dis. 8 (11): 698–709. doi:10.1016/S1473-3099(08)70255-X. PMID 18992406.
  16. ↑ Lu L, Li C, Hagedorn CH (2006). "Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis". Rev Med Virol. 16 (1): 5–36. doi:10.1002/rmv.482. PMID 16175650.
  17. ↑ Tei S, Kitajima N, Takahashi K, Mishiro S (2003). "Zoonotic transmission of hepatitis E virus from deer to human beings". Lancet. 362 (9381): 371–3. doi:10.1016/S0140-6736(03)14025-1. PMID 12907011.
  18. ↑ Colson P, Borentain P, Queyriaux B, Kaba M, Moal V, Gallian P; et al. (2010). "Pig liver sausage as a source of hepatitis E virus transmission to humans". J Infect Dis. 202 (6): 825–34. doi:10.1086/655898. PMID 20695796.
  19. ↑ Goens SD, Perdue ML (2004). "Hepatitis E viruses in humans and animals". Anim Health Res Rev. 5 (2): 145–56. PMID 15984321.
  20. ↑ Meng XJ (2010). "Recent advances in Hepatitis E virus". J Viral Hepat. 17 (3): 153–61. doi:10.1111/j.1365-2893.2009.01257.x. PMID 20040046.
  21. ↑ Meng XJ (2011). "From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety". Virus Res. 161 (1): 23–30. doi:10.1016/j.virusres.2011.01.016. PMC 3126906. PMID 21316404.
  22. ↑ Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y; et al. (2011). "Structural basis for the neutralization and genotype specificity of hepatitis E virus". Proc Natl Acad Sci U S A. 108 (25): 10266–71. doi:10.1073/pnas.1101309108. PMC 3121834. PMID 21642534.
  23. ↑ Legrand-Abravanel F, Mansuy JM, Dubois M, Kamar N, Peron JM, Rostaing L; et al. (2009). "Hepatitis E virus genotype 3 diversity, France". Emerg Infect Dis. 15 (1): 110–4. doi:10.3201/eid1501.080296. PMC 2660688. PMID 19116067.
  24. ↑ Purdy MA, Khudyakov YE (2010). "Evolutionary history and population dynamics of hepatitis E virus". PLoS One. 5 (12): e14376. doi:10.1371/journal.pone.0014376. PMC 3006657. PMID 21203540.
  25. ↑ Aggarwal R, Kini D, Sofat S, Naik SR, Krawczynski K (2000). "Duration of viraemia and faecal viral excretion in acute hepatitis E." Lancet. 356 (9235): 1081–2. doi:10.1016/S0140-6736(00)02737-9. PMID 11009149.
  26. ↑ Ippagunta SK, Naik S, Sharma B, Aggarwal R (2007). "Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern". J Med Virol. 79 (12): 1827–31. doi:10.1002/jmv.21017. PMID 17935174.
  27. ↑ 27.0 27.1 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.
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