Experimental infection of the laboratory rat with the hepatitis E virus

Maneerat, Yaowapa; Clayson, Edward T.; Myint, Khin Saw Aye; Young, G. David; Innis, Bruce L.

doi:10.1002/(sici)1096-9071(199602)48:2<121::aid-jmv1>3.3.co;2-c

Cited by 35 publications

(42 citation statements)

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“…Trials to experimentally infect laboratory rats or mice with human HEV led to contradictory results, because some studies reported successful infection and others did not. 27,28 Recently, an HEV-related agent was detected from wild rats, and sequence comparison to human and avian HEV strains revealed only 59.9% and 49.9% nucleotide identity, respectively. 29 The low nucleotide sequence identities between rat HEV and human HEV may indicate an independent evolution of both viruses with no transmission between both hosts.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis E Virus Infection among Animals and Humans in Xinjiang, China: Possibility of Swine to Human Transmission of Sporadic Hepatitis E in an Endemic Area

Li²,

Zhu³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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Abstract. Hepatitis E is a worldwide public health problem, especially in areas with poor sanitation. This study examines the potential hepatitis E virus (HEV) animal reservoirs and the current status of HEV infection among animals and humans in an endemic area of Xinjiang, China. One thousand five hundred twenty-one serum samples from 12 different animal species and 296 sera from humans were detected for anti-HEV with an in-house enzyme immunoassay, and partial HEV RNA was amplified with a reverse transcription-nested polymerase chain reaction (RT-nPCR). All these distinct animal species, except jerboa and hoptoad, were positive for anti-HEV. However, HEV RNA was only amplified from pigs and a sporadic hepatitis E case in humans. The human HEV strain (CHN-XJ-HE29) shared 100% nucleotide identity with the swine HEV strain (CHN-XJ-SW50), both of which were collected from the same district; this indicates the possibility of HEV transmission from swine to humans in an endemic area.

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Section: Discussionmentioning

confidence: 99%

Hepatitis E Virus Infection among Animals and Humans in Xinjiang, China: Possibility of Swine to Human Transmission of Sporadic Hepatitis E in an Endemic Area

Li²,

Zhu³

et al. 2010

The American Society of Tropical Medicine and Hygiene

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“…Trials to infect laboratory rats or mice experimentally with human HEV led to contradictory results, as some studies reported successful infection whilst others did not (Karetnyï et al, 1993;Li et al, 2008;Maneerat et al, 1996). Several studies have shown the detection of HEV-specific antibodies in rodents from different countries including India, Vietnam, Brazil, Japan and the USA, including commensal rodents such as Norway (Rattus norvegicus) and black (Rattus rattus) rats, but also wild rodents such as deer mouse (Peromyscus maniculatus) and cotton rat (Sigmodon hispidus) (Arankalle et al, 2001;Favorov et al, 2000;Hirano et al, 2003;Kabrane-Lazizi et al, 1999;Meng et al, 2002;Vitral et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…HEV-specific antibodies as well as viral RNA have been detected in several animal species (Smith, 2001;Meng, 2009 An initial indication for a potential role of rodents in the transmission of hepatitis E was found by the detection of HEV antigen in the sera of rodents caught next to a Russian village where an outbreak of hepatitis E was reported (Karetnyï et al, 1993). Trials to infect laboratory rats or mice experimentally with human HEV led to contradictory results, as some studies reported successful infection whilst others did not (Karetnyï et al, 1993;Li et al, 2008;Maneerat et al, 1996). Several studies have shown the detection of HEV-specific antibodies in rodents from different countries including India, Vietnam, Brazil, Japan and the USA, including commensal rodents such as Norway (Rattus norvegicus) and black (Rattus rattus) rats, but also wild rodents such as deer mouse (Peromyscus maniculatus) and cotton rat (Sigmodon hispidus) (Arankalle Favorov et al, 2000;Hirano et al, 2003;Kabrane-Lazizi et al, 1999; Meng et al, 2002;Vitral et al, 2005).…”

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confidence: 99%

Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR

Johne

Plenge‐Bönig

Heß

et al. 2009

Journal of General Virology

328

273

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Hepatitis E is a rare human disease in developed countries. It is caused by hepatitis E virus (HEV), which is probably transmitted zoonotically to humans from domestic pigs and wild boars. Multiple reports on the detection of HEV-specific antibodies in rats have suggested the presence of an HEV-related agent; however, infectious virus or a viral genome has not been demonstrated so far. Here, a nested broad-spectrum RT-PCR protocol was developed capable of detecting different HEV types including those derived from wild boar and chicken. Screening of 30 faecal samples from wild Norway rats (Rattus norvegicus) from Hamburg (Germany) resulted in the detection of two sequences with similarities to human, mammalian and avian HEV. Virus particles with a morphology reminiscent of HEV were demonstrated by immunoelectron microscopy in one of these samples and the virus was tentatively designated rat HEV. Genome fragments with sizes of 4019 and 1545 nt were amplified from two samples. Sequence comparison with human and avian strains revealed only 59.9 and 49.9 % sequence identity, respectively. Similarly, the deduced amino acid sequence for the complete capsid protein had 56.2 and 42.9 % identity with human and avian strains, respectively. Inoculation of the samples onto three different permanent rat liver cell lines did not result in detectable virus replication as assayed by RT-PCR with cells of the fifth virus passage. Further investigations are necessary to clarify the zoonotic potential of rat HEV and to assess its suitability to serve in a laboratory rat animal model for human hepatitis E. INTRODUCTIONHepatitis E, caused by hepatitis E virus (HEV), is a worldwide human disease that is endemic in many developing countries. In industrialized countries, sporadic cases are increasingly reported, which can be traced either to imported infections from endemic regions or to autochthonous HEV infections (Clemente-Casares et al., 2003;Dalton et al., 2008; Gyarmati et al., 2007;Purcell & Emerson, 2008). Hepatitis E is characterized by a selflimiting jaundice of varying severity, which is hard to distinguish from a hepatitis of other viral origin, and is often accompanied by non-specific symptoms such as fever, headache and pain in the upper abdomen. Although the case fatality rate of hepatitis E is low in the general population (0.5-3 %), rates of up to 20 % have been observed for pregnant women (Shrestha et al., 2007;Smith, 2001;Wichmann et al., 2008).HEV is classified as the only member of the genus Hepevirus. This genus is subdivided into four distinct genotypes and the avian HEV strains (Bilic et al., 2009), which are not included in any of the other genotypes. All mammalian HEV isolates described to date comprise the same serotype (Lu et al., 2006;Takahashi et al., 2005). The HEV virion appears as a non-enveloped icosahedral sphere of approximately 27-34 nm in diameter. The crystal structure of HEV-like particles has recently been solved (Yamashita et al., 2009). The particles are composed of a single capsid protein, whic...

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“…It has been suspected that HEV might replicate in tissues and organs other than the liver (2). Recent results from studies performed with rats infected with human HEV have suggested that the virus may replicate extrahepatically (20). The objectives of this study are to utilize swine as a model system to systematically study HEV replication and to identify potential extrahepatic sites of HEV replication.…”

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confidence: 99%

Evidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Model

et al. 2001

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Hepatitis E virus (HEV) is the major cause of enterically transmitted non-A, non-B hepatitis in many developing countries and is also endemic in many industrialized countries. Due to the lack of an effective cell culture system and a practical animal model, the mechanisms of HEV pathogenesis and replication are poorly understood. Our recent identification of swine HEV from pigs affords us an opportunity to systematically study HEV replication and pathogenesis in a swine model. In an early study, we experimentally infected specificpathogen-free pigs with two strains of HEV: swine HEV and the US-2 strain of human HEV. Eighteen pigs (group 1) were inoculated intravenously with swine HEV, 19 pigs (group 2) were inoculated with the US-2 strain of human HEV, and 17 pigs (group 3) were used as uninoculated controls. The clinical and pathological findings have been previously reported. In this expanded study, we aim to identify the potential extrahepatic sites of HEV replication using the swine model. Two pigs from each group were necropsied at 3, 7, 14, 20, 27, and 55 days postinoculation (DPI). Thirteen different types of tissues and organs were collected from each necropsied animal. Reverse transcriptase PCR (RT-PCR) was used to detect the presence of positive-strand HEV RNA in each tissue collected during necropsy at different DPI. A negative-strand-specific RT-PCR was standardized and used to detect the replicative, negative strand of HEV RNA from tissues that tested positive for the positive-strand RNA. As expected, positive-strand HEV RNA was detected in almost every type of tissue at some time point during the viremic period between 3 and 27 DPI. Positive-strand HEV RNA was still detectable in some tissues in the absence of serum HEV RNA from both swine HEV-and human HEVinoculated pigs. However, replicative, negative-strand HEV RNA was detected primarily in the small intestines, lymph nodes, colons, and livers. Our results indicate that HEV replicates in tissues other than the liver. The data from this study may have important implications for HEV pathogenesis, xenotransplantation, and the development of an in vitro cell culture system for HEV.Hepatitis E virus (HEV), the causative agent of hepatitis E, has been recognized as a major cause of enterically transmitted non-A, non-B hepatitis in many developing countries (1,30,37,39). Transmission of the virus occurs primarily by the fecal-oral route through contaminated drinking water in areas with poor sanitation. The disease affects mainly young adults, with a reported mortality rate of up to 25% for pregnant women (10, 14, 37, 39). In the United States, sporadic cases of acute hepatitis E without known risk factors have been documented and anti-HEV antibodies have been detected in a significant proportion of healthy individuals (21,28,32,37,39,45). HEV is a positive, single-stranded RNA virus without an envelope. The genome, which is about 7.5 kb in size, contains three open reading frames (ORFs) and a short 5Ј and 3Ј nontranslated region (13,18,31,38). ORF 1 is...

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Experimental infection of the laboratory rat with the hepatitis E virus

Cited by 35 publications

References 0 publications

Hepatitis E Virus Infection among Animals and Humans in Xinjiang, China: Possibility of Swine to Human Transmission of Sporadic Hepatitis E in an Endemic Area

Hepatitis E Virus Infection among Animals and Humans in Xinjiang, China: Possibility of Swine to Human Transmission of Sporadic Hepatitis E in an Endemic Area

Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR

Evidence of Extrahepatic Sites of Replication of the Hepatitis E Virus in a Swine Model

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