Advances in Animal and Veterinary Sciences

Download PDF Download ePUB
AAVS_MH20140929060940_Saxena

 

Review Article

 

Hepatitis E Virus Infection: A Zoonotic Threat

 

Vikas Saxena1, Sushrut Arora2

1Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, Missouri, USA; 2Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.

 

Abstract | Hepatitis E is a virus mediated liver disease caused by hepatitis E virus (HEV). There are an estimated 3 million cases of acute HEV infection every year, causing 70,000 hepatitis E-related deaths worldwide. HEV is transmitted via the fecal-oral route. Contaminated water and food are main source of infection. HEV is classified in the family Hepeviridae and divided in four putative genera. Genotype 1 and 2 are associated with epidemics in East and South Asia and restricted to humans, whereas genotypes 3 and 4 are zoonotic and associated with cluster cases of hepatitis E in developed countries. HEV strains were isolated from variety of animals and the demonstrated ability of cross-species infection by some of these animal strains have broadened the host range and raised the concern of zoonosis. Pigs, deer and other animal species may serve as a reservoir for HEV. This review highlights the current understanding of HEV infection in humans and animals.

 

Keywords | Hepatitis, Hepatitis E, Hepatitis E virus, Liver Disease, Zoonosis

 

Editor | Kuldeep Dhama, Indian Veterinary Research Institute, Uttar Pradesh, India.

Received | September 29, 2014; Revised | November 16, 2014; Accepted | November 18, 2014; Published | November 21, 2014

*Correspondence | Vikas Saxena, University of Missouri, Columbia, Missouri, USA; Email: vikassaxena79@gmail.com

Citation | Saxena V, Arora S (2014). Hepatitis E Virus infection: A Zoonotic threat. Adv. Anim. Vet. Sci. 2 (10): 582-591.

DOI | http://dx.doi.org/10.14737/journal.aavs/2014/2.10.582.591

ISSN (Online) | 2307-8316; ISSN (Print) | 2309-3331

Copyright © 2014 Saxena and Arora. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.>

 

 

Introduction

 

Hepatitis E, first recognized as non-A and non-B hepatitis more than three decades ago, is characterized by an acute hepatitis and poses a serious threat to human and animal health. According to a recent estimate each year there are more than 3 million symptomatic cases of acute hepatitis E, resulting in approximately 70,000 deaths worldwide (Rein et al., 2012). Hepatitis E is mainly attributed to poor hygienic conditions and consumption of contaminated or insufficiently treated drinking water (Benjelloun et al., 1997; Coursaget, et al., 1998a; Guthmann et al., 2006). Outbreaks of waterborne hepatitis E had been observed following heavy rainfall and flooding in endemic regions (Corwin et al., 1996; Piper-Jenks et al., 2000). However, on account of better hygiene and quality of water supply, industrialized countries were considered HEV free or non-endemic for HEV; but isolated incidence of disease outbreaks were reported in developed countries (Hoofnagle et al., 2012). Hepatitis E is self-limiting, i.e. gets cured without medical intervention, in immunocompetent individuals causing <2% mortality, but in immunocompromised patients chronic hepatitis could be induced and among pregnant women mortality could be high (10-30%) (Kumar et al., 2004b). Disease pathogenesis, though not fully understood, can lead to acute liver failure, chronic infection, or extrahepatic symptoms (Krain et al., 2014).

 

The causative agent, hepatitis E virus (HEV), is classified into the genus Hepevirus and family Hepeviridae. A new taxonomic scheme for the family Hepeviridae has recently been proposed (Smith et al., 2014). HEV genomic RNA is comprised of a short 5` non-coding region (NCR), three open reading frames (ORFs), and a 3` NCR. ORF1 encodes a polyprotein which is purportedly processed into methyltransferase domain, Y domain, papain-like cysteine protease, proline-rich hinge domain or variable protein, X domain linked to the viral papain-like proteases, RNA helicase and RNA polymerase. A subgenomic RNA is generated during viral replication which encodes ORF2, a capsid protein and ORF3, a small phosphorylated protein (Tam et al., 1991; Koonin et al., 1992; Holla et al., 2013).

 

HEV has been isolated and characterized from humans and variety of other animal species ranging from bats, chicken, camel, cutthroat trout, deer, ferret, fox, mink, mongoose, moose, pig, rabbit, rat and wild boar (Meng, 2010a; Meng, 2010b; Meng, 2011; Meng, 2013). With this expanding host range and diversity, hepatitis E is now recognized as a zoonotic disease for which animals like bats, pigs and other animal species may serve as reservoirs. Successful transmission of swine HEV to macaques and cases of acute and sometimes fatal hepatitis E following consumption of uncooked deer or wild boar meat highlight zoonotic potential of HEV infection (Tei et al., 2003; Takahashi et al., 2004; Tei et al., 2004; Li et al., 2005). Further establishment of chronic hepatitis E, as a result of persistent HEV infection in an immunocompromised individual indicates potential huge burden on health care expenditure and warrants urgent intervention towards curtailing zoonotic transfer of HEV (Kamar et al., 2008; Kamar et al., 2011). Here emerging zoonotic risks of HEV induced hepatitis E are reviewed and a potential strategy to prevent zoonosis has been proposed.

 

Hepatitis E in Human

Hepatitis E in human is an acute, self-limiting illness, with symptoms generally clearing off within weeks and in some cases, within months of onset of infection. Hepatitis E is presented with symptoms related to other viral hepatitis infections in general and with those seen in acute hepatitis A in particular (Khuroo, 1980). Clinically, HEV infection is presented with combinations of symptoms such as fever, lassitude/weakness, fatigue, loss of appetite, nausea and/or vomiting, dark urine, light (clay/ash-colored) stool, hepatalgia, jaundice (yellowing of the skin and sclera) and hepatomegaly (Dalton et al., 2008; Terzic et al., 2009; Labrique et al., 2010; Aggarwal, 2011; Goumba et al., 2011) . Elevated level of alanine amino transferase, aspartate transaminase, and gamma-glutamyl transpeptidase are common indicator of hepatic infection of hepatitis E (Terzic et al., 2009; Turner et al., 2010).

 

HEV infections in both epidemic- and sporadic-transmission settings are mostly asymptomatic and subclinical in different geographic regions (Nicand et al., 2001; Khuroo et al., 2004; Guthmann et al., 2006; Stoszek et al., 2006; Dalton et al., 2007; Christensen et al., 2008; Begum et al., 2009; Kuniholm et al., 2009; Gad et al., 2011; Renou et al., 2011; Aggarwal, 2013). Sporadic cases of hepatitis E in industrialized countries were mainly associated with travel to endemic countries such as India, Mexico, Nepal and Pakistan (Centers for Disease Control and Prevention, 1993; Johansson et al., 1995; La Rosa et al., 2011). However, autochthonous cases of acute HEV infection in patients who had never travelled to endemic regions were also reported (Schlauder et al., 1998; Schlauder et al., 1999; Ijaz et al., 2009). Cases of HEV infections without overt symptoms were documented in organ donors (Schlosser et al., 2012) and in associates of infected patients (Renou et al., 2011). Some of the hepatitis E patients may progress to acute liver failure (ALF), also called fulminant hepatic failure, which is often fatal if onset is within 6 to 8 weeks of first symptom. Pregnant women and patients with preexisting chronic liver illnesses are at increased risk of developing ALF (Coursaget et al., 1998b; Ghoshal et al., 2001; Kumar et al., 2004a; Mamun et al., 2009). Rarely, HEV infections may be prolonged or chronic, mainly among patients with compromised immune systems and patients receiving immunosuppressive drugs during organ transplant or cancer therapy (Khuroo et al., 2004; Matsubayashi et al., 2004; Mitsui et al., 2004; Boxall et al., 2006; Colson et al., 2007; Tamura et al., 2007; Matsubayashi et al., 2008; Mansuy et al., 2009; Schlosser et al., 2012). These reports indicate that HEV infection is more prevalent than originally believed. A considerably large number of people were found to be anti-HEV antibody positive e.g. 19-21% of blood donors in USA (Thomas et al., 1997; Xu et al., 2013), 13-53% subjects studied in European countries (Ijaz et al., 2009; Mansuy et al., 2011; Romano et al., 2011; Faber et al., 2012) and 6-43% subjects studied in Asian countries (Li et al., 2006; Dong et al., 2007; Taniguchi et al., 2009; Chiu et al., 2013; Lee et al., 2013) had antibodies specific to HEV.

 

Hepatitis E in animals

 

Bats

Drexler et al. (2012) had analysed 3,869 bat specimens from 85 different species and from five continents for hepevirus RNA. Presence of HEV RNA was confirmed in bats originating from Africa, Central America and Europe. Despite this widespread distribution of HEV in bats, none of the bat hepevirus transmission to human could be confirmed in over 90,000 human blood donations and individual patient sera, indicative of limited zoonotic potential for bat hepevirus. Based on sequence comparison a new genus for bat HEV has been proposed.

 

Camel

Woo et al. (2014) had detected presence of HEV RNA in fecal samples from 3 dromedary camels in Dubai, United Arab Emirates. On the basis of sequence analysis, less than 20% nucleotide similarity was found when compared with known HEV and therefore author proposed a new genus for dromedary camel HEV (dcHEV).

 

Chicken

At least three genotypes of HEV have been documented from chickens worldwide (Bilic et al., 2009; Marek et al., 2010). HEV infection in chickens is enzootic affecting 71% of chicken flocks in the United States. HEV infection in chickens is mostly subclinical, while 30% of chickens were seropositive for avian HEV antibodies (Huang et al., 2002; Sun et al., 2004). Though evidence of avian infection in humans is currently lacking (Huang et al., 2004), but spread of bird to bird infection had been reported (Hsu and Tsai, 2014).

 

Cut throat trout (Fish)

Fish HEV virus was originally described as the cutthroat trout (Oncorhynchus clarkii) virus (CTV) (Batts et al., 2011). CTV was isolated from spawning adult trout in the United States. Based on genome organization and nucleotide sequence virus was linked to Hepeviridae family. However CTV shares only 13-27% amino acid sequence identity with human or avian HEV. So far it is the only HEV isolate which could efficiently be propagated in the Chinook salmon embryo (CHSE-214) cell line.

 

Ferrets

Ferret strain of HEV (FRHEV) was genetically identified in the Netherlands and in the laboratory ferrets in Japan (Raj et al., 2012; Li et al., 2014). Ferret HEV isolate from the Netherlands was distinct from HEV genotype 1-4, and shared the highest nucleotide identity (72.3%) with rat HEV. Ferret HEV genome organization was also different from known HEV genotypes owing to the existence of ORF4 as an overlapping region of ORF1. FRHEV isolate from laboratory ferret in Japan shares 82.4%-82.5% nucleotide identity with the Netherlands strain and ORF2 shares 94.2%-94.8% amino acid identity, indicative of similar antigenicity.

 

Fox

Bodewes et al. (2013), in their attempt to study viral microbiome in red foxes (Vulpes vulpes), evaluated fecal samples of 13 red foxes by random PCR and sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses and picobirnaviruses, were detected. Fox hepevirus shared highest amino acid homology (73%-85%) with rat HEV.

 

Mink

Krog et al. (2013) had evaluated fecal and liver samples of farmed mink in Denmark. Following initial screening from 85 fecal samples of farmed mink by nested PCR they developed a RT-PCR based assay and further examined 233 samples from total 89 animals. Phylogenetic analysis of viral sequence placed farmed mink HEV together with ferret and rat HEV, with 76% and 69% nucleotide sequence identity, respectively. A 65% identity with HEV genotype 3 and 4 was identified.

 

Moose

Moose are common animal hunted for consumption in the whole of Scandinavia. Lin et al. (2014) examined liver sample of a three-year old deceased moose for the presence of HEV RNA. Identified sequence was highly divergent from known four HEV genotypes (1-4) with nucleotide sequence similarity of 37-63%.

 

Domestic Pig

Swine hepatitis E virus (swine HEV) was the first identified animal strain of HEV. It was isolated from domestic pigs in the United States (Meng et al., 1997). Swine HEV belongs to HEV genotype 3 and 4, and was identified worldwide. HEV infection in pigs is also through fecal-oral route and fecal shedding of virus is the major source of virus for spread among both pigs as well as humans (Meng, 2013).

 

Wild Boar

Wild boars (Sus scrofa) was reported to harbor HEV in Spain (de Deus et al., 2008), Germany (Kaci et al., 2008), Italy (Martelli et al., 2008), Japan (Michitaka et al., 2007; Takahashi et al., 2011), and Australia (Chandler et al., 1999). These wild boars generally were detected to be infected with HEV genotype 3 and 4.

 

Rats

Rat HEV shares only 60% and 50% sequence homology with other mammalian and avian strain of HEV, respectively. Various strains of HEV were genetically identified in wild and domestic species of rat (Johne et al., 2010a; Johne et al., 2010b; Purcell et al., 2011; Johne et al., 2012). With recent identification of HEV genotype 3 strains from rats in United States, zoonotic potential of rat HEV has gained importance.

 

Rabbits

Rabbit HEV shares 74% nucleotide homology with HEV genotype 1, 73% with genotype 2, 78% to 79% with genotype 3, 74% to 75% with genotype 4 and 46% to 47% with avian HEV. Related HEV strains were isolated from rabbits in China (Zhao et al., 2009), United States (Cossaboom et al., 2011), and France (Izopet et al., 2012). Experimentally, rabbit HEV strain was successfully demonstrated to be transmitted to pigs, indicative of crossing species barrier (Cossaboom et al., 2012).

 

Other Potential Animal Reservoirs

Anti-HEV antibodies and HEV RNA amplicon were detected in other animals such as cattle, sheep, dog, deer, cat, goat and nonhuman primates (Meng, 2013). Detection of HEV infection in variety of these animal species suggest a widespread circulation of HEV and phylogenetic analysis of these virus isolates will help in comprehending the host range and existing animal reservoirs of HEV.

 

HEV Crossing Species Barrier

HEV genotype 1 and 2 are mostly restricted to humans as seen from unsuccessful experimental infection of pigs (Meng et al., 1998a) and goats (Sanford et al., 2013) with HEV. However, HEV genotype 3 and 4 had infected both nonhuman primates and pigs (Meng et al., 1998b; Halbur et al., 2001; Williams et al., 2001; Feagins et al., 2008). Zoonotic transmission of HEV from deer (Tei et al., 2003; Tei et al., 2004) and pet cat (Kuno et al., 2003) to humans had also been reported. Recent rise in cases of persistent HEV infection in immunocompromised patients had almost exclusively found to be infected with HEV genotype 3 (Kamar et al., 2012), suggesting zoonotic mode of infection transmission (Legrand-Abravanel et al., 2010; Moal et al., 2012).

 

 

Diagnosis

 

As mentioned before, hepatitis E symptoms are clinically indistinguishable from other types of acute viral hepatitis. Therefore, diagnosis of HEV infection is usually based on the detection of virus specific IgA, IgG, and IgM antibodies in blood. Virus specific antibodies are generally detected against ORF2 protein based ELISA test (Ghabrah et al., 1998; Engle et al., 2002; Meng et al., 2002). Anti-HEV IgG antibody detection assay systems are commercially available from Abbott Laboratories, Wiesbaden, Germany (Abbott Immunoglobulin G Assay) and Genelabs Diagnostitics, Singapore (Genelabs IgG Assay). Both assays were found to have adequate sensitivity and specificity in a hepatitis outbreak setting (Myint et al., 2006). Detection of anti-HEV IgA and IgM is indicative of recent infection, however, detection of HEV RNA in serum, bile and/or fecal samples is the most reliable marker of an ongoing HEV infection. HEV RNA is detected by nucleic acid amplification technique-based reverse transcriptase polymerase chain reaction (RT-PCR) in a qualitative assay (presence or absence of viral RNA in a biological sample), or quantitative assay (copy number of viral RNA per ml of biological specimen). World Health Organization (WHO) established an international standard candidate for HEV RNA, code number 6329/10, formulated by using a genotype 3a HEV strain and is available in lyophilized form to be used as a positive candidate in quantitative RT-PCR assay for calculation of copy number from patient specimen (Baylis et al., 2013).

 

 

Treatment and Prevention

 

As HEV is a self-limiting disease, no line of treatment is available and disease prevention is the best method. In 2011, first vaccine against HEV infection, Hecolin or HEV-239, in human was licensed in China (Wu et al., 2012; Zhang et al., 2013). This vaccine is not yet available in rest of the world. In the absence of vaccine, availability of clean water and good hygiene practices such as washing hands properly and consumption of only properly cooked food will be very helpful in controlling virus spread.

 

 

Perspective

 

With accumulating evidence it is clear that HEV is no more limited to only developing countries. HEV is now recognized as infectious agent affecting humans and animals and therefore posing a serious public health threat worldwide. Zoonotic transmission of HEV is the major cause of hepatitis E in developed countries. Despite presence of HEV across the world, this pathogen remains relatively neglected on the global public health stage. Lack of medical and laboratory infrastructure and lack of awareness of HEV hinders surveillance of virus spread. With recent availability of sensitive diagnostic assays it is important that all the tools, necessary to identify and respond to HEV infections, made available in different parts of the world. A detailed guideline to follow up infection cases in endemic as well as in emergency situation needs to be developed to contain virus. Active research on hepatitis E both in animal and human had given novel insights into the HEV pathogenesis, yet more work is needed to understand chronic and extra-hepatic infections to be able to determine better treatment approaches. Similarly, an understanding of disease pathogenesis in pregnant women and children will be helpful in addressing global impact of HEV. Availability of human vaccine in all parts of the world and development of an effective animal HEV vaccine is need of the hour to prevent spread of infection across different species and to human.

 

 

References

 

  • Aggarwal R (2011). Clinical presentation of hepatitis E. Virus Res. 161(1): 15-22. http://dx.doi.org/10.1016/j.virusres.2011.03.017
  •  

  • Aggarwal R (2013). Hepatitis E: clinical presentation in disease-endemic areas and diagnosis. Semin. Liver. Dis. 33(1): 30-40. http://dx.doi.org/10.1055/s-0033-1338112
  •  

  • Batts W, Yun S, Hedrick R, Winton J (2011). A novel member of the family Hepeviridae from cutthroat trout (Oncorhynchus clarkii). Virus Res. 158(1-2): 116-123. http://dx.doi.org/10.1016/j.virusres.2011.03.019
  •  

  • Baylis SA, Blumel J, Mizusawa S, Matsubayashi K, Sakata H, Okada Y, Nubling CM, Hanschmann KM, Group HEVCS (2013). World Health Organization International Standard to harmonize assays for detection of hepatitis E virus RNA. Emerg. Infect. Dis. 19(5): 729-735. http://dx.doi.org/10.3201/eid1905.121845
  •  

  • Begum N, Devi SG, Husain SA, Ashok K, Kar P (2009). Seroprevalence of subclinical HEV infection in pregnant women from north India: a hospital based study. Indian J. Med. Res. 130(6): 709-713.
  •  

  • Benjelloun S, Bahbouhi B, Bouchrit N, Cherkaoui L, Hda N, Mahjour J, Benslimane A (1997). Seroepidemiological study of an acute hepatitis E outbreak in Morocco. Res. Virol. 148(4): 279-287. http://dx.doi.org/10.1016/S0923-2516(97)88365-3
  •  

  • Bilic I, Jaskulska B, Basic A, Morrow CJ, Hess M (2009). Sequence analysis and comparison of avian hepatitis E viruses from Australia and Europe indicate the existence of different genotypes. J. Gen. Virol. 90(4): 863-873. http://dx.doi.org/10.1099/vir.0.007179-0
  •  

  • Bodewes R, van der Giessen J, Haagmans BL, Osterhaus AD, Smits SL (2013). Identification of multiple novel viruses, including a parvovirus and a hepevirus, in feces of red foxes. J. Virol. 87(13): 7758-7764. http://dx.doi.org/10.1128/JVI.00568-13
  •  

  • Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, Teo CG (2006). Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus. Med. 16(2): 79-83. http://dx.doi.org/10.1111/j.1365-3148.2006.00652.x
  •  

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

  • Chandler JD, Riddell MA, Li F, Love RJ, Anderson DA (1999). Serological evidence for swine hepatitis E virus infection in Australian pig herds. Vet. Microbiol. 68(1-2): 95-105. http://dx.doi.org/10.1016/S0378-1135(99)00065-6
  •  

  • Chiu DM, Chan MC, Yeung AC, Ngai KL, Chan PK (2013). Seroprevalence of hepatitis E virus in Hong Kong, 2008-2009. J. Med. Virol. 85(3): 459-461. http://dx.doi.org/10.1002/jmv.23429
  •  

  • Christensen PB, Engle RE, Hjort C, Homburg KM, Vach W, Georgsen J, Purcell RH (2008). Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin. Infect. Dis. 47(8): 1026-1031. http://dx.doi.org/10.1086/591970
  •  

  • Colson P, Coze C, Gallian P, Henry M, De Micco P, Tamalet C (2007). Transfusion-associated hepatitis E, France. Emerg. Infect. Dis. 13(4): 648-649. http://dx.doi.org/10.3201/eid1304.061387
  •  

  • Corwin AL, Khiem HB, Clayson ET, Pham KS, Vo TT, Vu TY, Cao TT, Vaughn D, Merven J, Richie TL, Putri MP, He J, Graham R, Wignall FS, Hyams KC (1996). A waterborne outbreak of hepatitis E virus transmission in southwestern Vietnam. Am. J. Trop. Med. Hyg. 54(6): 559-562.
  •  

  • Cossaboom CM, Cordoba L, Dryman BA, Meng XJ (2011). Hepatitis E virus in rabbits, Virginia, USA. Emerg. Infect. Dis. 17(11): 2047-2049. http://dx.doi.org/10.3201/eid1711.110428
  •  

  • 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(8): 1687-1695. http://dx.doi.org/10.1099/vir.0.041509-0
  •  

  • Coursaget P, Buisson Y, Enogat N, Bercion R, Baudet JM, Delmaire P, Prigent D, Desrame J (1998a). Outbreak of enterically-transmitted hepatitis due to hepatitis A and hepatitis E viruses. J. Hepatol. 28(5): 745-750. http://dx.doi.org/10.1016/S0168-8278(98)80222-5
  •  

  • Coursaget P, Buisson Y, N’Gawara MN, Van Cuyck-Gandre H, Roue R (1998b). Role of hepatitis E virus in sporadic cases of acute and fulminant hepatitis in an endemic area (Chad). Am. J. Trop. Med. Hyg. 58(3): 330-334.
  •  

  • Dalton HR, Stableforth W, Thurairajah P, Hazeldine S, Remnarace R, Usama W, Farrington L, Hamad N, Sieberhagen C, Ellis V, Mitchell J, Hussaini SH, Banks M, Ijaz S, Bendall RP (2008). Autochthonous hepatitis E in southwest England: natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. Eur. J. Gastroenterol. Hepatol. 20(8): 784-790. http://dx.doi.org/10.1097/MEG.0b013e3282f5195a
  •  

  • Dalton HR, Thurairajah PH, Fellows HJ, Hussaini HS, Mitchell J, Bendall R, Banks M, Ijaz S, Teo CG, Levine DF (2007). Autochthonous hepatitis E in southwest England. J. Viral Hepat. 14(5): 304-309. http://dx.doi.org/10.1111/j.1365-2893.2006.00800.x
  •  

  • de Deus N, Peralta B, Pina S, Allepuz A, Mateu E, Vidal D, Ruiz-Fons F, Martin M, Gortazar C, Segales J (2008). Epidemiological study of hepatitis E virus infection in European wild boars (Sus scrofa) in Spain. Vet. Microbiol. 129(1-2): 163-170. http://dx.doi.org/10.1016/j.vetmic.2007.11.002
  •  

  • Dong C, Dai X, Shao JS, Hu K, Meng JH (2007). Identification of genetic diversity of hepatitis E virus (HEV) and determination of the seroprevalence of HEV in eastern China. Arch. Virol. 152(4): 739-746. http://dx.doi.org/10.1007/s00705-006-0882-0
  •  

  • 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(17): 9134-9147. http://dx.doi.org/10.1128/JVI.00800-12
  •  

  • Engle RE, Yu C, Emerson SU, Meng XJ, Purcell RH (2002). Hepatitis E virus (HEV) capsid antigens derived from viruses of human and swine origin are equally efficient for detecting anti-HEV by enzyme immunoassay. J. Clin. Microbiol. 40(12): 4576-4580. http://dx.doi.org/10.1128/JCM.40.12.4576-4580.2002
  •  

  • Faber MS, Wenzel JJ, Jilg W, Thamm M, Hohle M, Stark K (2012). Hepatitis E virus seroprevalence among adults, Germany. Emerg. Infect. Dis. 18(10): 1654-1657. http://dx.doi.org/10.3201/eid1810.111756
  •  

  • Feagins AR, Opriessnig T, Huang YW, Halbur PG, Meng XJ (2008). Cross-species infection of specific-pathogen-free pigs by a genotype 4 strain of human hepatitis E virus. J. Med. Virol. 80(8): 1379-1386. http://dx.doi.org/10.1002/jmv.21223
  •  

  • Gad YZ, Mousa N, Shams M, Elewa A (2011). Seroprevalence of subclinical HEV infection in asymptomatic, apparently healthy, pregnant women in Dakahlya Governorate, Egypt. Asian J. Transfus. Sci. 5(2): 136-139. http://dx.doi.org/10.4103/0973-6247.83238
  •  

  • Ghabrah TM, Tsarev S, Yarbough PO, Emerson SU, Strickland GT, Purcell RH (1998). Comparison of tests for antibody to hepatitis E virus. J. Med. Virol. 55(2): 134-137. http://dx.doi.org/10.1002/(SICI)1096-9071(199806)55:2<134::AID-JMV9>3.3.CO;2-H
  •  

  • Ghoshal UC, Somani S, Chetri K, Akhtar P, Aggarwal R, Naik SR (2001). Plasmodium falciparum and hepatitis E virus co-infection in fulminant hepatic failure. Indian J. Gastroenterol. 20(3): 111.
  •  

  • Goumba AI, Konamna X, Komas NP (2011). Clinical and epidemiological aspects of a hepatitis E outbreak in Bangui, Central African Republic. BMC Infect. Dis. 11: 93. http://dx.doi.org/10.1186/1471-2334-11-93
  •  

  • Guthmann JP, Klovstad H, Boccia D, Hamid N, Pinoges L, Nizou JY, Tatay M, Diaz F, Moren A, Grais RF, Ciglenecki I, Nicand E, Guerin PJ (2006). A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin. Infect. Dis. 42(12): 1685-1691. http://dx.doi.org/10.1086/504321
  •  

  • Halbur PG, Kasorndorkbua C, Gilbert C, Guenette D, Potters MB, Purcell RH, Emerson SU, Toth TE, Meng XJ (2001). Comparative pathogenesis of infection of pigs with hepatitis E viruses recovered from a pig and a human. J. Clin. Microbiol. 39(3): 918-923. http://dx.doi.org/10.1128/JCM.39.3.918-923.2001
  •  

  • Holla RP, Ahmad I, Ahmad Z, Jameel S (2013). Molecular virology of hepatitis E virus. Semin. Liver. Dis. 33(1): 3-14. http://dx.doi.org/10.1055/s-0033-1338110
  •  

  • Hoofnagle JH, Nelson KE, Purcell RH (2012). Hepatitis E. N. Engl. J. Med. 367(13):1237-1244. http://dx.doi.org/10.1056/NEJMra1204512
  •  

  • Hsu IW, Tsai HJ (2014). Avian hepatitis E virus in chickens, Taiwan, 2013. Emerg. Infect. Dis. 20(1): 149-151. http://dx.doi.org/10.3201/eid2001.131224
  •  

  • Huang FF, Haqshenas G, Shivaprasad HL, Guenette DK, Woolcock PR, Larsen CT, Pierson FW, Elvinger F, Toth TE, Meng XJ (2002). Heterogeneity and seroprevalence of a newly identified avian hepatitis e virus from chickens in the United States. J. Clin. Microbiol. 40(11): 4197-4202. http://dx.doi.org/10.1128/JCM.40.11.4197-4202.2002
  •  

  • Huang FF, Sun ZF, Emerson SU, Purcell RH, Shivaprasad HL, Pierson FW, Toth TE, Meng XJ (2004). 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. 85(6): 1609-1618. http://dx.doi.org/10.1099/vir.0.79841-0
  •  

  • Ijaz S, Vyse AJ, Morgan D, Pebody RG, Tedder RS, Brown D (2009). Indigenous hepatitis E virus infection in England: more common than it seems. J. Clin. Virol. 44(4): 272-276. http://dx.doi.org/10.1016/j.jcv.2009.01.005
  •  

  • 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(8): 1274-1281. http://dx.doi.org/10.3201/eid1808.120057
  •  

  • Johansson PJ, Mushahwar IK, Norkrans G, Weiland O, Nordenfelt E (1995). Hepatitis E virus infections in patients with acute hepatitis non-A-D in Sweden. Scand. J. Infect. Dis. 27(6): 543-546. http://dx.doi.org/10.3109/00365549509047064
  •  

  • Johne R, Dremsek P, Kindler E, Schielke A, Plenge-Bonig A, Gregersen H, Wessels U, Schmidt K, Rietschel W, Groschup MH, Guenther S, Heckel G, Ulrich RG (2012). Rat hepatitis E virus: geographical clustering within Germany and serological detection in wild Norway rats (Rattus norvegicus). Infect. Genet. Evol. 12(5): 947-956. http://dx.doi.org/10.1016/j.meegid.2012.02.021
  •  

  • Johne R, Heckel G, Plenge-Bonig A, Kindler E, Maresch C, Reetz J, Schielke A, Ulrich RG (2010a). Novel hepatitis E virus genotype in Norway rats, Germany. Emerg. Infect. Dis. 16(9): 1452-1455. http://dx.doi.org/10.3201/eid1609.100444
  •  

  • Johne R, Plenge-Bonig A, Hess M, Ulrich RG, Reetz J, Schielke A (2010b). Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR. J. Gen. Virol. 91(3): 750-758. http://dx.doi.org/10.1099/vir.0.016584-0
  •  

  • Kaci S, Nockler K, Johne R (2008). Detection of hepatitis E virus in archived German wild boar serum samples. Vet. Microbiol. 128(3-4): 380-385. http://dx.doi.org/10.1016/j.vetmic.2007.10.030
  •  

  • Kamar N, Garrouste C, Haagsma EB, Garrigue V, Pischke S, Chauvet C, Dumortier J, Cannesson A, Cassuto-Viguier E, Thervet E, Conti F, Lebray P, Dalton HR, Santella R, Kanaan N, Essig M, Mousson C, Radenne S, Roque-Afonso AM, Izopet J, Rostaing L (2011). Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 140(5): 1481-1489. http://dx.doi.org/10.1053/j.gastro.2011.02.050
  •  

  • Kamar N, Selves J, Mansuy JM, Ouezzani L, Peron JM, Guitard J, Cointault O, Esposito L, Abravanel F, Danjoux M, Durand D, Vinel JP, Izopet J, Rostaing L (2008). Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N. Engl. J. Med. 358(8): 811-817. http://dx.doi.org/10.1056/NEJMoa0706992
  •  

  • Kamar N, Weclawiak H, Guilbeau-Frugier C, Legrand-Abravanel F, Cointault O, Ribes D, Esposito L, Cardeau-Desangles I, Guitard J, Sallusto F, Muscari F, Peron JM, Alric L, Izopet J, Rostaing L (2012). Hepatitis E virus and the kidney in solid-organ transplant patients. Transplantation 93(6): 617-623.
  •  

  • 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(6): 818-824. http://dx.doi.org/10.1016/0002-9343(80)90200-4
  •  

  • Khuroo MS, Kamili S, Yattoo GN (2004). Hepatitis E virus infection may be transmitted through blood transfusions in an endemic area. J. Gastroenterol. Hepatol. 19(7): 778-784. http://dx.doi.org/10.1111/j.1440-1746.2004.03437.x
  •  

  • 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(17): 8259-8263. http://dx.doi.org/10.1073/pnas.89.17.8259
  •  

  • Krain LJ, Nelson KE, Labrique AB (2014). Host immune status and response to hepatitis E virus infection. Clin. Microbiol. Rev. 27(1): 139-165. http://dx.doi.org/10.1128/CMR.00062-13
  •  

  • Krog JS, Breum SO, Jensen TH, Larsen LE (2013). Hepatitis E virus variant in farmed mink, Denmark. Emerg. Infect. Dis. 19(12): 2028-2030. http://dx.doi.org/10.3201/eid1912.130614
  •  

  • Kumar A, Aggarwal R, Naik SR, Saraswat V, Ghoshal UC, Naik S (2004a). Hepatitis E virus is responsible for decompensation of chronic liver disease in an endemic region. Indian J. Gastroenterol. 23(2): 59-62.
  •  

  • Kumar A, Beniwal M, Kar P, Sharma JB, Murthy NS (2004b). Hepatitis E in pregnancy. Int. J. Gynaecol. Obstet. 85(3): 240-244. http://dx.doi.org/10.1016/j.ijgo.2003.11.018
  •  

  • Kuniholm MH, Purcell RH, McQuillan GM, Engle RE, Wasley A, Nelson KE (2009). Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988-1994. J. Infect. Dis. 200(1): 48-56. http://dx.doi.org/10.1086/599319
  •  

  • Kuno A, Ido K, Isoda N, Satoh Y, Ono K, Satoh S, Inamori H, Sugano K, Kanai N, Nishizawa T, Okamoto H (2003). Sporadic acute hepatitis E of a 47-year-old man whose pet cat was positive for antibody to hepatitis E virus. Hepatol. Res. 26(3): 237-242. http://dx.doi.org/10.1016/S1386-6346(03)00197-9
  •  

  • La Rosa G, Muscillo M, Vennarucci VS, Garbuglia AR, La Scala P, Capobianchi MR (2011). Hepatitis E virus in Italy: molecular analysis of travel-related and autochthonous cases. J. Gen. Virol. 92(7): 1617-1626. http://dx.doi.org/10.1099/vir.0.031278-0
  •  

  • Labrique AB, Zaman K, Hossain Z, Saha P, Yunus M, Hossain A, Ticehurst JR, Nelson KE (2010). Epidemiology and risk factors of incident hepatitis E virus infections in rural Bangladesh. Am. J. Epidemiol. 172(8): 952-961. http://dx.doi.org/10.1093/aje/kwq225
  •  

  • Lee JT, Shao PL, Chang LY, Xia NS, Chen PJ, Lu CY, Huang LM (2013). Seroprevalence of Hepatitis E Virus Infection among Swine Farmers and the General Population in Rural Taiwan. PLoS ONE 8(6): e67180. http://dx.doi.org/10.1371/journal.pone.0067180
  •  

  • Legrand-Abravanel F, Kamar N, Sandres-Saune K, Garrouste C, Dubois M, Mansuy JM, Muscari F, Sallusto F, Rostaing L, Izopet J (2010). Characteristics of autochthonous hepatitis E virus infection in solid-organ transplant recipients in France. J. Infect. Dis. 202(6): 835-844. http://dx.doi.org/10.1086/655899
  •  

  • Li RC, Ge SX, Li YP, Zheng YJ, Nong Y, Guo QS, Zhang J, Ng MH, Xia NS (2006). Seroprevalence of hepatitis E virus infection, rural southern People’s Republic of China. Emerg. Infect. Dis. 12(11): 1682-1688. http://dx.doi.org/10.3201/eid1211.060332
  •  

  • Li TC, Chijiwa K, Sera N, Ishibashi T, Etoh Y, Shinohara Y, Kurata Y, Ishida M, Sakamoto S, Takeda N, Miyamura T (2005). Hepatitis E virus transmission from wild boar meat. Emerg. Infect. Dis. 11(12): 1958-1960. http://dx.doi.org/10.3201/eid1112.051041
  •  

  • Li TC, Yang T, Ami Y, Suzaki Y, Shirakura M, Kishida N, Asanuma H, Takeda N, Takaji W (2014). Complete genome of hepatitis E virus from laboratory ferrets. Emerg. Infect. Dis. 20(4): 709-712. http://dx.doi.org/10.3201/eid2004.131815
  •  

  • Lin J, Norder H, Uhlhorn H, Belak S, Widen F (2014). Novel hepatitis E like virus found in Swedish moose. J. Gen. Virol. 95(3): 557-570. http://dx.doi.org/10.1099/vir.0.059238-0
  •  

  • Mamun Al M, Rahman S, Khan M, Karim F (2009). HEV infection as an aetiologic factor for acute hepatitis: experience from a tertiary hospital in Bangladesh. J. Health Popul. Nutr. 27(1): 14-19.
  •  

  • Mansuy JM, Bendall R, Legrand-Abravanel F, Saune K, Miedouge M, Ellis V, Rech H, Destruel F, Kamar N, Dalton HR, Izopet J (2011). Hepatitis E virus antibodies in blood donors, France. Emerg. Infect. Dis. 17(12): 2309-2312. http://dx.doi.org/10.3201/eid1712.110371
  •  

  • Mansuy JM, Huynh A, Abravanel F, Recher C, Peron JM, Izopet J (2009). Molecular evidence of patient-to-patient transmission of hepatitis E virus in a hematology ward. Clin. Infect. Dis. 48(3): 373-374. http://dx.doi.org/10.1086/595893
  •  

  • Marek A, Bilic I, Prokofieva I, Hess M (2010). 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. 145(1-2): 54-61. http://dx.doi.org/10.1016/j.vetmic.2010.03.014
  •  

  • Martelli F, Caprioli A, Zengarini M, Marata A, Fiegna C, Di Bartolo I, Ruggeri FM, Delogu M, Ostanello F (2008). Detection of hepatitis E virus (HEV) in a demographic managed wild boar (Sus scrofa scrofa) population in Italy. Vet. Microbiol. 126(1-3): 74-81. http://dx.doi.org/10.1016/j.vetmic.2007.07.004
  •  

  • Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, Sato S, Kato T, Nishimori H, Tsuji K, Maguchi H, Yoshida J, Maekubo H, Mishiro S, Ikeda H (2008). A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route. Transfusion 48(7): 1368-1375. http://dx.doi.org/10.1111/j.1537-2995.2008.01722.x
  •  

  • Matsubayashi K, Nagaoka Y, Sakata H, Sato S, Fukai K, Kato T, Takahashi K, Mishiro S, Imai M, Takeda N, Ikeda H (2004). Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion 44(6): 934-940. http://dx.doi.org/10.1111/j.1537-2995.2004.03300.x
  •  

  • Meng XJ (2010a). Hepatitis E virus: animal reservoirs and zoonotic risk. Vet. Microbiol. 140(3-4): 256-265. http://dx.doi.org/10.1016/j.vetmic.2009.03.017
  •  

  • Meng XJ (2010b). Recent advances in Hepatitis E virus. J. Viral Hepat. 17(3): 153-161. http://dx.doi.org/10.1111/j.1365-2893.2009.01257.x
  •  

  • 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. http://dx.doi.org/10.1016/j.virusres.2011.01.016
  •  

  • Meng XJ (2013). Zoonotic and foodborne transmission of hepatitis E virus. Semin. Liver. Dis. 33(1):41-49. http://dx.doi.org/10.1055/s-0033-1338113
  •  

  • Meng XJ, Halbur PG, Haynes JS, Tsareva TS, Bruna JD, Royer RL, Purcell RH, Emerson SU (1998a). Experimental infection of pigs with the newly identified swine hepatitis E virus (swine HEV), but not with human strains of HEV. Arch. Virol. 143(7): 1405-1415. http://dx.doi.org/10.1007/s007050050384
  •  

  • Meng XJ, Halbur PG, Shapiro MS, Govindarajan S, Bruna JD, Mushahwar IK, Purcell RH, Emerson SU (1998b). Genetic and experimental evidence for cross-species infection by swine hepatitis E virus. J. Virol. 72(12): 9714-9721.
  •  

  • 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(18): 9860-9865. http://dx.doi.org/10.1073/pnas.94.18.9860
  •  

  • Meng XJ, Wiseman B, Elvinger F, Guenette DK, Toth TE, Engle RE, Emerson SU, Purcell RH (2002). 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. 40(1): 117-122. http://dx.doi.org/10.1128/JCM.40.1.117-122.2002
  •  

  • Michitaka K, Takahashi K, Furukawa S, Inoue G, Hiasa Y, Horiike N, Onji M, Abe N, Mishiro S (2007). Prevalence of hepatitis E virus among wild boar in the Ehime area of western Japan. Hepatol. Res. 37(3): 214-220. http://dx.doi.org/10.1111/j.1872-034X.2007.00030.x
  •  

  • Mitsui T, Tsukamoto Y, Yamazaki C, Masuko K, Tsuda F, Takahashi M, Nishizawa T, Okamoto H (2004). Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion. J. Med. Virol. 74(4): 563-572. http://dx.doi.org/10.1002/jmv.20215
  •  

  • Moal V, Gerolami R, Colson P (2012). First human case of co-infection with two different subtypes of hepatitis E virus. Intervirology 55(6): 484-487. http://dx.doi.org/10.1159/000335664
  •  

  • Myint KS, Endy TP, Gibbons RV, Laras K, Mammen MP, Jr., Sedyaningsih ER, Seriwatana J, Glass JS, Narupiti S, Corwin AL (2006). Evaluation of diagnostic assays for hepatitis E virus in outbreak settings. J. Clin. Microbiol. 44(4): 1581-1583. http://dx.doi.org/10.1128/JCM.44.4.1581-1583.2006
  •  

  • Nicand E, Grandadam M, Teyssou R, Rey JL, Buisson Y (2001). Viraemia and faecal shedding of HEV in symptom-free carriers. Lancet 357(9249): 68-69. http://dx.doi.org/10.1016/S0140-6736(05)71568-3
  •  

  • Piper-Jenks N, Horowitz HW, Schwartz E (2000). Risk of hepatitis E infection to travelers. J. Travel. Med. 7(4): 194-199. http://dx.doi.org/10.2310/7060.2000.00059
  •  

  • Purcell RH, Engle RE, Rood MP, Kabrane-Lazizi Y, Nguyen HT, Govindarajan S, St Claire M, Emerson SU (2011). Hepatitis E virus in rats, Los Angeles, California, USA. Emerg. Infect. Dis. 17(12): 2216-2222. http://dx.doi.org/10.3201/eid1712.110482
  •  

  • Raj VS, Smits SL, Pas SD, Provacia LB, Moorman-Roest H, Osterhaus AD, Haagmans BL (2012). Novel hepatitis E virus in ferrets, the Netherlands. Emerg. Infect. Dis. 18(8): 1369-1370. http://dx.doi.org/10.3201/eid1808.111659
  •  

  • Rein DB, Stevens GA, Theaker J, Wittenborn JS, Wiersma ST (2012). The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology 55(4): 988-997. http://dx.doi.org/10.1002/hep.25505
  •  

  • Renou C, Pariente A, Cadranel JF, Nicand E, Pavio N (2011). Clinically silent forms may partly explain the rarity of acute cases of autochthonous genotype 3c hepatitis E infection in France. J. Clin. Virol. 51(2): 139-141. http://dx.doi.org/10.1016/j.jcv.2011.02.013
  •  

  • Romano L, Paladini S, Tagliacarne C, Canuti M, Bianchi S, Zanetti AR (2011). Hepatitis E in Italy: a long-term prospective study. J. Hepatol. 54(1): 34-40. http://dx.doi.org/10.1016/j.jhep.2010.06.017
  •  

  • Sanford BJ, Emerson SU, Purcell RH, Engle RE, Dryman BA, Cecere TE, Buechner-Maxwell V, Sponenberg DP, Meng XJ (2013). Serological evidence for a hepatitis e virus-related agent in goats in the United States. Transbound. Emerg. Dis. 60(6): 538-545. http://dx.doi.org/10.1111/tbed.12001
  •  

  • 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 (3): 447-456.
  •  

  • Schlauder GG, Desai SM, Zanetti AR, Tassopoulos NC, Mushahwar IK (1999). Novel hepatitis E virus (HEV) isolates from Europe: evidence for additional genotypes of HEV. J. Med. Virol. 57(3): 243-251. http://dx.doi.org/10.1002/(SICI)1096-9071(199903)57:3<243::AID-JMV6>3.0.CO;2-R
  •  

  • Schlosser B, Stein A, Neuhaus R, Pahl S, Ramez B, Kruger DH, Berg T, Hofmann J (2012). Liver transplant from a donor with occult HEV infection induced chronic hepatitis and cirrhosis in the recipient. J. Hepatol. 56(2): 500-502. http://dx.doi.org/10.1016/j.jhep.2011.06.021
  •  

  • Smith DB, Simmonds P, members of the International Committee on the 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(10): 2223-2232. http://dx.doi.org/10.1099/vir.0.068429-0
  •  

  • Stoszek SK, Engle RE, Abdel-Hamid M, Mikhail N, Abdel-Aziz F, Medhat A, Fix AD, Emerson SU, Purcell RH, Strickland GT (2006). Hepatitis E antibody seroconversion without disease in highly endemic rural Egyptian communities. Trans. R. Soc. Trop. Med. Hyg. 100(2): 89-94. http://dx.doi.org/10.1016/j.trstmh.2005.05.019
  •  

  • Sun ZF, Larsen CT, Dunlop A, Huang FF, Pierson FW, Toth TE, Meng XJ (2004). Genetic identification of avian hepatitis E virus (HEV) from healthy chicken flocks and characterization of the capsid gene of 14 avian HEV isolates from chickens with hepatitis-splenomegaly syndrome in different geographical regions of the United States. J. Gen. Virol. 85(3): 693-700. http://dx.doi.org/10.1099/vir.0.19582-0
  •  

  • 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(2): 501-505. http://dx.doi.org/10.1016/j.virol.2004.10.006
  •  

  • Takahashi M, Nishizawa T, Sato H, Sato Y, Jirintai, Nagashima S, Okamoto H (2011). Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype. J. Gen. Virol. 92(4): 902-908. http://dx.doi.org/10.1099/vir.0.029470-0
  •  

  • 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(1): 120-131. http://dx.doi.org/10.1016/0042-6822(91)90760-9
  •  

  • Tamura A, Shimizu YK, Tanaka T, Kuroda K, Arakawa Y, Takahashi K, Mishiro S, Shimizu K, Moriyama M (2007). Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma. Hepatol. Res. 37(2): 113-120. http://dx.doi.org/10.1111/j.1872-034X.2007.00024.x
  •  

  • Taniguchi M, Kim SR, Mishiro S, Takahashi K, Shin MH, Yun H, Park MS, Li ZM, Kim MK, Fang J, Hayashi Y (2009). Epidemiology of hepatitis E in Northeastern China, South Korea and Japan. J. Infect. 58(3): 232-237. http://dx.doi.org/10.1016/j.jinf.2009.01.011
  •  

  • Tei S, Kitajima N, Ohara S, Inoue Y, Miki M, Yamatani T, Yamabe H, Mishiro S, Kinoshita Y (2004). 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. 74(1): 67-70. http://dx.doi.org/10.1002/jmv.20147
  •  

  • Tei S, Kitajima N, Takahashi K, Mishiro S (2003). Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet 362(9381): 371-373. http://dx.doi.org/10.1016/S0140-6736(03)14025-1
  •  

  • Terzic D, Dupanovic B, Mugosa B, Draskovic N, Svirtlih N (2009). Acute hepatitis E in Montenegro: epidemiology, clinical and laboratory features. Ann. Hepatol. 8(3): 203-206.
  • Thomas DL, Yarbough PO, Vlahov D, Tsarev SA, Nelson KE, Saah AJ, Purcell RH (1997). Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J. Clin. Microbiol. 35(5): 1244-1247.
  •  

  • Turner J, Godkin A, Neville P, Kingham J, Ch’ng CL (2010). Clinical characteristics of hepatitis E in a “Non-Endemic” population. J. Med. Virol. 82(11): 1899-1902. http://dx.doi.org/10.1002/jmv.21905
  •  

  • Williams TP, Kasorndorkbua C, Halbur PG, Haqshenas G, Guenette DK, Toth TE, Meng XJ (2001). Evidence of extrahepatic sites of replication of the hepatitis E virus in a swine model. J. Clin. Microbiol. 39(9): 3040-3046. http://dx.doi.org/10.1128/JCM.39.9.3040-3046.2001
  •  

  • 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(6): 1044-1048. http://dx.doi.org/10.3201/eid2006.140140
  •  

  • Wu T, Li SW, Zhang J, Ng MH, Xia NS, Zhao Q (2012). Hepatitis E vaccine development: a 14 year odyssey. Hum. Vaccin. Immunother. 8(6): 823-827. http://dx.doi.org/10.4161/hv.20042
  •  

  • Xu C, Wang RY, Schechterly CA, Ge S, Shih JW, Xia NS, Luban NL, Alter HJ (2013). 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 53(10pt2): 2505-2511. http://dx.doi.org/10.1111/trf.12326
  •  

  • Zhang J, Shih JW, Wu T, Li SW, Xia NS (2013). Development of the hepatitis E vaccine: from bench to field. Semin. Liver Dis. 33(1): 79-88. http://dx.doi.org/10.1055/s-0033-1338116
  •  

  • 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(8): 1371-1379. http://dx.doi.org/10.1002/jmv.21536
  •