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| __NOTOC__
| | #REDIRECT[[Hepatitis E Virus]] |
| {{Hepatitis E}}
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| {{CMG}}; {{AE}} {{JS}}
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| ==Overview==
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| The [[hepatitis E virus]] ([[HEV]]) is the causative agent of hepatitis E. It is a member of the [[genus]] [[Hepevirus]] that belongs to the Hepeviridae family. It is a nonenveloped, single-stranded positive-sense [[RNA]] virus. The [[genome]] of [[HEV]] contains 3 [[Open reading frame]]s: [[ORF]] 1, [[ORF]] 2, and [[ORF]] 3. The [[RNA]] [[genome]] acts as a template for [[viral replication]], structural and nonstructural [[protein synthesis]]. Five different [[genotype]]s have been identified, all belonging to the same [[serotype]]. Depending on the [[genotype]], epidemiological and clinical manifestations will be different: [[genotype]]s 1 and 2 only cause disease in humans, and are transmitted through water and [[fecal-oral route]], while [[genotype]]s 3 and 4 cause disease in animals, having humans as accidental hosts, and are transmitted through the consumption of undercook meat. The [[HEV]] replicates within the host cell's [[cytoplasm]], however, its [[cellular]] [[receptor]], and mechanism of entry remain unknown.
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| ==Taxonomy==
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| [[Virus]]es; ssRNA viruses; ssRNA positive-strand viruses; Hepeviridae; [[Hepevirus]]; [[Hepatitis E virus]]<ref name=NCBI>{{cite web | title = Hepatitis E virus taxonomy | url = http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=12461 }}</ref>
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| ==Biology==
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| {| style="float: right;"
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| | [[File:HEV.jpg|200px|thumb|none|Hepatitis E virus <SMALL>''[http://phil.cdc.gov/phil/details.asp Centers for Disease Control and Prevention]''<ref>{{Cite web | title = http://phil.cdc.gov/phil/details.asp | url = http://phil.cdc.gov/phil/details.asp}}</ref></SMALL>]]
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| |}
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| The viral particles are 27 to 34 [[nanometer]]s in diameter, [[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.<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref><ref name="pmid2107574">{{cite journal| author=Reyes GR, Purdy MA, Kim JP, Luk KC, Young LM, Fry KE et al.| title=Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. | journal=Science | year= 1990 | volume= 247 | issue= 4948 | pages= 1335-9 | pmid=2107574 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2107574 }} </ref><ref name="pmid1926770">{{cite journal| author=Tam AW, Smith MM, Guerra ME, Huang CC, Bradley DW, Fry KE et al.| title=Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. | journal=Virology | year= 1991 | volume= 185 | issue= 1 | pages= 120-31 | pmid=1926770 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1926770 }} </ref>
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| The genome of [[HEV]] contains 3 [[Open reading frame]]s:
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| *'''ORF1''' - encodes functional motifs and non-structural [[protein]] domains for [[replication]] and [[protein]] processing, including:<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref><ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref>
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| :*[[Cysteine]] [[protease]]
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| :*[[Methyltransferase]]
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| :*[[RNA]] [[helicase]]
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| :*[[RNA]]-dependent [[RNA]] [[polymerase]]
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| *'''ORF2''' - encodes the protein of the [[viral capsid]], with neutralizing [[epitopes]], responsible for:<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075 }} </ref>
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| :*Assembly of [[virions]]<ref name="pmid9311793">{{cite journal| author=Li TC, Yamakawa Y, Suzuki K, Tatsumi M, Razak MA, Uchida T et al.| title=Expression and self-assembly of empty virus-like particles of hepatitis E virus. | journal=J Virol | year= 1997 | volume= 71 | issue= 10 | pages= 7207-13 | pmid=9311793 | doi= | pmc=PMC192060 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9311793 }} </ref>
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| :*Target cell interaction<ref name="pmid19812150">{{cite journal| author=Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S| title=Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. | journal=J Virol | year= 2009 | volume= 83 | issue= 24 | pages= 12714-24 | pmid=19812150 | doi=10.1128/JVI.00717-09 | pmc=PMC2786843 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19812150 }} </ref>
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| :*[[Immunogenicity]]<ref name="pmid21068233">{{cite journal| author=Xing L, Wang JC, Li TC, Yasutomi Y, Lara J, Khudyakov Y et al.| title=Spatial configuration of hepatitis E virus antigenic domain. | journal=J Virol | year= 2011 | volume= 85 | issue= 2 | pages= 1117-24 | pmid=21068233 | doi=10.1128/JVI.00657-10 | pmc=PMC3020005 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21068233 }} </ref>
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| :*Mutations in the [[viral capsid]] may attenuate the [[HEV|virus]] and lead to the development of a [[vaccine]]
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| *'''ORF3''' - encodes a small protein involved in the [[morphogenesis]] and release of the [[virion]]s.<ref name="pmid19339479">{{cite journal| author=Yamada K, Takahashi M, Hoshino Y, Takahashi H, Ichiyama K, Nagashima S et al.| title=ORF3 protein of hepatitis E virus is essential for virion release from infected cells. | journal=J Gen Virol | year= 2009 | volume= 90 | issue= Pt 8 | pages= 1880-91 | pmid=19339479 | doi=10.1099/vir.0.010561-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19339479 }} </ref><ref name="pmid20610720">{{cite journal| author=Emerson SU, Nguyen HT, Torian U, Burke D, Engle R, Purcell RH| title=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. | journal=J Virol | year= 2010 | volume= 84 | issue= 18 | pages= 9059-69 | pmid=20610720 | doi=10.1128/JVI.00593-10 | pmc=PMC2937629 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20610720 }} </ref>
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| ===Genotypes===
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| In order to study the [[biology]] of the [[virus]] and develop new treatment drugs, [[HEV]] must be grown in culture systems, such as:
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| *PLC/PRF/5 cell line of hepatic carcinoma, A549 cell line of lung carcinoma, and fecal samples from an infected patient<ref name="pmid17325363">{{cite journal| author=Tanaka T, Takahashi M, Kusano E, Okamoto H| title=Development and evaluation of an efficient cell-culture system for Hepatitis E virus. | journal=J Gen Virol | year= 2007 | volume= 88 | issue= Pt 3 | pages= 903-11 | pmid=17325363 | doi=10.1099/vir.0.82535-0 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17325363 }} </ref>
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| *HepG2/C3A cell line of hepatoma<ref name="pmid21262830">{{cite journal| author=Shukla P, Nguyen HT, Torian U, Engle RE, Faulk K, Dalton HR et al.| title=Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. | journal=Proc Natl Acad Sci U S A | year= 2011 | volume= 108 | issue= 6 | pages= 2438-43 | pmid=21262830 | doi=10.1073/pnas.1018878108 | pmc=PMC3038723 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21262830 }} </ref>
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| Molecular studies of [[HEV]] lead to the classification of the [[HEV|virus]] into 4 [[genotype]]s:<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref><ref name="pmid18992406">{{cite journal| author=Dalton HR, Bendall R, Ijaz S, Banks M| title=Hepatitis E: an emerging infection in developed countries. | journal=Lancet Infect Dis | year= 2008 | volume= 8 | issue= 11 | pages= 698-709 | pmid=18992406 | doi=10.1016/S1473-3099(08)70255-X | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18992406 }} </ref><ref name="pmid16175650">{{cite journal| author=Lu L, Li C, Hagedorn CH| title=Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. | journal=Rev Med Virol | year= 2006 | volume= 16 | issue= 1 | pages= 5-36 | pmid=16175650 | doi=10.1002/rmv.482 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16175650 }} </ref><ref name="pmid12907011">{{cite journal| author=Tei S, Kitajima N, Takahashi K, Mishiro S| title=Zoonotic transmission of hepatitis E virus from deer to human beings. | journal=Lancet | year= 2003 | volume= 362 | issue= 9381 | pages= 371-3 | pmid=12907011 | doi=10.1016/S0140-6736(03)14025-1 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12907011 }} </ref><ref name="pmid20695796">{{cite journal| author=Colson P, Borentain P, Queyriaux B, Kaba M, Moal V, Gallian P et al.| title=Pig liver sausage as a source of hepatitis E virus transmission to humans. | journal=J Infect Dis | year= 2010 | volume= 202 | issue= 6 | pages= 825-34 | pmid=20695796 | doi=10.1086/655898 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20695796 }} </ref><ref name="pmid22537448">{{cite journal| author=Wedemeyer H, Pischke S, Manns MP| title=Pathogenesis and treatment of hepatitis e virus infection. | journal=Gastroenterology | year= 2012 | volume= 142 | issue= 6 | pages= 1388-1397.e1 | pmid=22537448 | doi=10.1053/j.gastro.2012.02.014 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22537448 }} </ref><ref name="pmid15984321">{{cite journal| author=Goens SD, Perdue ML| title=Hepatitis E viruses in humans and animals. | journal=Anim Health Res Rev | year= 2004 | volume= 5 | issue= 2 | pages= 145-56 | pmid=15984321 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15984321 }} </ref><ref name="pmid20040046">{{cite journal| author=Meng XJ| title=Recent advances in Hepatitis E virus. | journal=J Viral Hepat | year= 2010 | volume= 17 | issue= 3 | pages= 153-61 | pmid=20040046 | doi=10.1111/j.1365-2893.2009.01257.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20040046 }} </ref><ref name="pmid21316404">{{cite journal| author=Meng XJ| title=From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. | journal=Virus Res | year= 2011 | volume= 161 | issue= 1 | pages= 23-30 | pmid=21316404 | doi=10.1016/j.virusres.2011.01.016 | pmc=PMC3126906 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21316404 }} </ref>
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| {| style="border: 2px solid #DCDCDC; font-size: 90%; width: 50%;"
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| |+ '''Genotypes'''
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| |-
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| ! style="width: 75px; background: #4479BA; text-align: center;"|{{fontcolor|#FFF|Genotype}}
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| ! style="width: 200px; background: #4479BA; text-align: center;"| {{fontcolor|#FFF|Characteristics}}
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| | style="background: #F5F5F5; padding: 5px; text-align: center;"| '''HEV1'''
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| | style="background: #DCDCDC; padding: 5px;"|
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| *Restricted to humans
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| *Responsible for [[epidemic]] hepatitis
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| *Water-borne disease in developing countries
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| *[[Fecal-oral route]] of [[transmission]]
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| *Predominant in Asia ([[endemic]] and [[epidemic]])
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| *Classified in 4 subgenotypes
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| |-
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| | style="background: #F5F5F5; padding: 5px; text-align: center;"| '''HEV2'''
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| | style="background: #DCDCDC; padding: 5px;"|
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| *Restricted to humans
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| *Responsible for [[epidemic]] hepatitis
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| *Water-borne disease in developing countries
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| *[[Fecal-oral route]] of [[transmission]]
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| *Predominant in Central America and Africa
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| *Classified in 2 subgenotypes
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| |-
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| | style="background: #F5F5F5; padding: 5px; text-align: center;"| '''HEV3'''
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| | style="background: #DCDCDC; padding: 5px;"|
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| *Infects humans (accidental host) and other mammalian species, such as pigs, deer, shellfish and rodents ([[zoonosis]])
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| *Responsible for autochthonous hepatitis E in developed and developing countries
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| *Worldwide distribution
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| *Consumption of undercooked pork
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| *Classified in 3 subgenotypes
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| *Important [[zoonotic]] [[transmission]]
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| |-
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| | style="background: #F5F5F5; padding: 5px; text-align: center;"| '''HEV4'''
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| | style="background: #DCDCDC; padding: 5px;"|
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| *Infects humans (accidental host) and other mammalian species, such as pigs, deer, shellfish and rodents ([[zoonosis]])
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| *Responsible for autochthonous hepatitis E in developed and developing countries
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| *Most frequent in southeast Asia
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| *Consumption of undercooked pork
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| *Classified in 7 subgenotypes
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| *Important [[zoonotic]] [[transmission]]
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| |-
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| | style="background: #F5F5F5; padding: 5px; text-align: center;"| '''HEV5'''
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| | style="background: #DCDCDC; padding: 5px;"|
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| *Recently identified in birds (''Avian HEV'')
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| |}
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| Despite the [[epidemiological]] and clinical differences, the different [[genotype]]s are thought to belong to one same [[serotype]], after studies with cross-[[neutralization]].<ref name="pmid21642534">{{cite journal| author=Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y et al.| title=Structural basis for the neutralization and genotype specificity of hepatitis E virus. | journal=Proc Natl Acad Sci U S A | year= 2011 | volume= 108 | issue= 25 | pages= 10266-71 | pmid=21642534 | doi=10.1073/pnas.1101309108 | pmc=PMC3121834 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21642534 }} </ref> Evidence shows that [[HEV]] has evolved and adapted to a series of hosts, until finally being able to [[infect]] humans. [[HEV]] subgenotypes in humans and pigs have been associated, also suggesting [[zoonotic]] [[transmission]].<ref name="pmid22549046">{{cite journal| author=Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J et al.| title=Hepatitis E. | journal=Lancet | year= 2012 | volume= 379 | issue= 9835 | pages= 2477-88 | pmid=22549046 | doi=10.1016/S0140-6736(11)61849-7 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22549046 }} </ref><ref name="pmid19116067">{{cite journal| author=Legrand-Abravanel F, Mansuy JM, Dubois M, Kamar N, Peron JM, Rostaing L et al.| title=Hepatitis E virus genotype 3 diversity, France. | journal=Emerg Infect Dis | year= 2009 | volume= 15 | issue= 1 | pages= 110-4 | pmid=19116067 | doi=10.3201/eid1501.080296 | pmc=PMC2660688 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19116067 }} </ref><ref name="pmid21203540">{{cite journal| author=Purdy MA, Khudyakov YE| title=Evolutionary history and population dynamics of hepatitis E virus. | journal=PLoS One | year= 2010 | volume= 5 | issue= 12 | pages= e14376 | pmid=21203540 | doi=10.1371/journal.pone.0014376 | pmc=PMC3006657 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21203540 }} </ref>
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| ===Life Cycle===
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| 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. Different recombination events may lead to changes in [[viral replication]], tissue [[tropism]] and [[pathogenesis]] of the [[HEV|virus]].<ref name="pmid23013075">{{cite journal| author=Hoofnagle JH, Nelson KE, Purcell RH| title=Hepatitis E. | journal=N Engl J Med | year= 2012 | volume= 367 | issue= 13 | pages= 1237-44 | pmid=23013075 | doi=10.1056/NEJMra1204512 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23013075 }} </ref>
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| ==Tropism==
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| Hepatitis D shows [[tropism]] for [[hepatocytes]], however, the host [[cell receptor]] has not been identified.<ref name="pmid19812150">{{cite journal| author=Kalia M, Chandra V, Rahman SA, Sehgal D, Jameel S| title=Heparan sulfate proteoglycans are required for cellular binding of the hepatitis E virus ORF2 capsid protein and for viral infection. | journal=J Virol | year= 2009 | volume= 83 | issue= 24 | pages= 12714-24 | pmid=19812150 | doi=10.1128/JVI.00717-09 | pmc=PMC2786843 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19812150 }} </ref>
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| ==Natural Reservoir==
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| The [[natural reservoir]] of [[HEV]] is yet to be identified. Different observations have suggested different reservoirs:
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| *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.<ref name="pmid11009149">{{cite journal| author=Aggarwal R, Kini D, Sofat S, Naik SR, Krawczynski K| title=Duration of viraemia and faecal viral excretion in acute hepatitis E. | journal=Lancet | year= 2000 | volume= 356 | issue= 9235 | pages= 1081-2 | pmid=11009149 | doi=10.1016/S0140-6736(00)02737-9 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11009149 }} </ref>
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| *Environmental reservoir was suggested following detection of [[HEV]] in sewages.<ref name="pmid17935174">{{cite journal| author=Ippagunta SK, Naik S, Sharma B, Aggarwal R| title=Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern. | journal=J Med Virol | year= 2007 | volume= 79 | issue= 12 | pages= 1827-31 | pmid=17935174 | doi=10.1002/jmv.21017 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17935174 }} </ref>
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| *Continuous fecal shedding from [[asymptomatic]] patients was suggested as a form of maintenance of the [[HEV|virus]], contaminating water supplies.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref>
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| *The existence of an animal reservoir is supported by the detection of anti-[[HEV]] antibodies in different animal species.<ref name="pmid21932388">{{cite journal| author=Aggarwal R, Jameel S| title=Hepatitis E. | journal=Hepatology | year= 2011 | volume= 54 | issue= 6 | pages= 2218-26 | pmid=21932388 | doi=10.1002/hep.24674 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21932388 }} </ref>
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| ==References==
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| {{reflist|2}}
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| [[Category:Hepatitis|E]]
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| [[Category:Viruses]]
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| [[Category:Infectious disease]]
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| [[Category:Gastroenterology]]
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