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 Courtesy: *Centers for Disease Control and Prevention*^[2]

The viral particles are 27 to 34 nanometers in diameter, are non-enveloped 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:

ORF1 - encodes functional motifs and non-structural protein domains, for replication and protein processing, including:^[3]^[6]

ORF2 - encodes de protein of the viral capsid, responsible for:

Assembly of virions^[7]
Target cell interaction^[8]
Immunogenicity^[9]
Mutations in the viral capsid may attenuate the virus and lead to the development of a vaccine

ORF3 - encodes a small protein involved in the morphogenesis and release of the virions.^[10]^[11]

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^[12]
HepG2/C3A cell line of hepatoma^[13]

Genotypes

Molecular studies of HEV lead to the classification of the virus into 4 genotypes:^[3]^[14]^[15]^[16]^[17]

**Genotypes**
Genotype	Symptoms
HEV1	Restricted to humans Water-borne disease in developing countries Predominant in Asia Classified in 4 subgenotypes
HEV2	Restricted to humans Water-borne disease in developing countries Predominant in Mexico and Africa Classified in 2 subgenotypes
HEV3	Infects humans and other mammalian species, such as pigs Responsible for autochthonous hepatitis E in developed and developing countries Worldwide distribution Consumption of undercooked pork Classified in 3 subgenotypes
HEV4	Infects humans and other mammalian species, such as pigs Responsible for autochthonous hepatitis E in developed and developing countries Most frequent in southeast Asia Consumption of undercooked pork Classified in 7 subgenotypes

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]^[18]^[19]

The cellular receptor for HEV and the mode of entry of the virus into the host cell are yet to be identified.^[8]

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.^[20]
Environmental reservoir was suggested following detection of HEV in sewages.^[21]
Continuous fecal shedding from asymptomatic patients was suggested as a form of maintenance of the virus, contaminating water supplies.^[22]
The existence of an animal reservoir is supported by the detection of anti-HEV antibodies in different species.^[22]

References

↑ "Hepatitis E virus taxonomy".
↑ "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)
↑ ^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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ ^8.0 ^8.1 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.
↑ 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.CS1 maint: PMC format (link)
↑ 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.
↑ 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.
↑ ^22.0 ^22.1 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.

[NCBI-1] "Hepatitis E virus taxonomy".

[2] "http://phil.cdc.gov/phil/details.asp". External link in |title= (help)

[pmid22549046-3] 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.

[pmid2107574-4] 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.

[pmid1926770-5] 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.

[pmid22537448-6] 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.

[pmid9311793-7] 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.

[pmid19812150-8] 8.0 ^8.1 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.

[pmid21068233-9] 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.

[pmid19339479-10] 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.

[pmid20610720-11] 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.

[pmid17325363-12] 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.

[pmid21262830-13] 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.

[pmid18992406-14] 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.

[pmid16175650-15] 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.

[pmid12907011-16] 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.

[pmid20695796-17] 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.

[pmid19116067-18] 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.

[pmid21203540-19] 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.CS1 maint: PMC format (link)

[pmid11009149-20] 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.

[pmid17935174-21] 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.

[pmid21932388-22] 22.0 ^22.1 Aggarwal R, Jameel S (2011). "Hepatitis E." Hepatology. 54 (6): 2218–26. doi:10.1002/hep.24674. PMID 21932388.

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