The use of non-human primates as animal models for the study of hepatitis viruses

Vitral, Cláudia Lamarca; Yoshida, Clara Fumiko Tachibana; Gaspar, Ana

doi:10.1590/s0100-879x1998000800003

Cited by 20 publications

(17 citation statements)

References 105 publications

(84 reference statements)

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“…For human hepatitis E, HEV infections of monkeys, pigs and chicken have been tested as animal models (Billam et al, 2005;Huang et al, 2007;Pudupakam et al, 2009;Vitral et al, 1998). Recently, HEV infection of BALB/c nude mice carrying a severe Tcell defect was described .…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…Since increases in liver enzyme levels are not typical in every case of hepatitis A and do not correlate well with the degree of liver cell damage [Vitral et al, 1998], the liver was examined for histopathological changes after necropsy 60 days post-infection. In the liver of all animals inoculated with HAV, except P9 G , hepatocyte swelling and rounding was a common feature ( Fig.…”

Section: Liver Pathologymentioning

confidence: 99%

“…It is believed that under natural conditions, HAV can infect only humans and certain species of nonhuman primates [Balayan, 1992]. This restricted host range has led to the establishment of primate animal models as well as cell culture systems of primate origin for studying HAV [Vitral et al, 1998;Provost and Hilleman, 1979]. The animal models used most commonly are chimpanzees (Pan troglodytes) [Dienstag et al, 1975[Dienstag et al, , 1976Popper et al, 1980], marmosets (Saguinus mystax) [Mathiesen et al, 1980;Krawczynski et al, 1981] and owl monkeys (Aotus trivirgatus) [LeDuc et al, 1983;Keenan et al, 1984;Trahan et al, 1987;Asher et al, 1995].…”

Section: Introductionmentioning

confidence: 99%

Experimental hepatitis A virus infection in guinea pigs

Hornei

Kämmerer

Moubayed

et al. 2001

Journal of Medical Virology

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Although many of the properties of hepatitis A virus (HAV) are known, several aspects of HAV pathogenesis are still not understood, such as the mechanism underlying the hepatotropism or HAV replication in extrahepatic sites. Detailed studies of these aspects were hampered mostly by the lack of accessible animal models, since only nonhuman primates are susceptible to experimental infections. An alternative animal model would also be of interest to assess the primary replication site and for the evaluation of the safety and efficacy of vaccines. A study was undertaken to determine whether HAV can infect guinea pigs and whether they are useful as a model for studying aspects of HAV pathogenesis and for the evaluation of vaccines. HAV variants adapted to primate or guinea pig tissue culture were used to inoculate guinea pigs intraperitoneally and by the oral route. The animals were observed for clinical disease, shedding of HAV in stools, viremia, seroconversion, evidence for liver damage by biochemical liver function tests, virus presence in the liver, development of hepatic histopathological changes, and occurrence of HAV in extrahepatic organs. The animals developed an active, clinically inapparent infection with specific histopathological changes in the liver. Although virus replication occurred, as shown by RT-PCR and isolation of infectious virus from feces and serum, it seems unlikely that guinea pigs are suitable for studying the clinical features of hepatitis A, because the clinical and laboratory parameters remained normal. However, guinea pigs appear useful for studying some aspects of HAV pathogenesis and for testing the safety of vaccines.

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“…Enterically transmitted hepatitis viruses (hepatitis A virus and hepatitis E virus) can induce hepatitis in a number of old world and new world monkey species. The host range of primates susceptible to hepatitis viruses transmitted by the parenteral route is restricted to a few species of old world monkeys and apes (Vitral et al 1998 Competitive ELISA was performed using hepatitis A virus ELISA kit (Wanti Hep. AV) to detect hepatitis A virus antibodies.…”

mentioning

confidence: 99%

Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

Nath¹,

Chakraborty²,

Sarma³

et al. 2013

J. Threat. Taxa

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The use of non-human primates as animal models for the study of hepatitis viruses

Cited by 20 publications

References 105 publications

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

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

Experimental hepatitis A virus infection in guinea pigs

Seroprevalence of Hepatitis A virus infection in non-human primates in Assam, India

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