An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 1. Validity of the Chimpanzee Model

Bailey, Jarrod

doi:10.1177/026119291003800501

Cited by 14 publications

(19 citation statements)

References 309 publications

(433 reference statements)

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“…It has especially been shown that therapeutic vaccines including structural proteins are better T cell stimulators than vaccines where only non-structural proteins are present (Dahari et al, 2010). But so far, it was not possible to clearly identify a safe and effective vaccine for humans (Bailey, 2010). …”

Section: Naturally Hcv Permissive Animal Modelsmentioning

confidence: 99%

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Mailly¹,

Robinet²,

Meuleman³

et al. 2013

Front. Microbiol.

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Hepatitis C virus (HCV) is a major cause of cirrhosis and hepatocellular carcinoma (HCC) making the virus the most common cause of liver failure and transplantation. HCV is estimated to chronically affect 130 million individuals and to lead to more than 350,000 deaths per year worldwide. A vaccine is currently not available. The recently developed direct acting antivirals (DAAs) have markedly increased the efficacy of the standard of care but are not efficient enough to completely cure all chronically infected patients and their toxicity limits their use in patients with advanced liver disease, co-morbidity or transplant recipients. Because of the host restriction, which is limited to humans and non-human primates, in vivo study of HCV infection has been hampered since its discovery more than 20 years ago. The chimpanzee remains the most physiological model to study the innate and adaptive immune responses, but its use is ethically difficult and is now very restricted and regulated. The development of a small animal model that allows robust HCV infection has been achieved using chimeric liver immunodeficient mice, which are therefore not suitable for studying the adaptive immune responses. Nevertheless, these models allowed to go deeply in the comprehension of virus-host interactions and to assess different therapeutic approaches. The immunocompetent mouse models that were recently established by genetic humanization have shown an interesting improvement concerning the study of the immune responses but are still limited by the absence of the complete robust life cycle of the virus. In this review, we will focus on the relevant available animal models of HCV infection and their usefulness for deciphering the HCV life cycle and virus-induced liver disease, as well as for the development and evaluation of new therapeutics. We will also discuss the perspectives on future immunocompetent mouse models and the hurdles to their development.

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Section: Naturally Hcv Permissive Animal Modelsmentioning

confidence: 99%

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Mailly¹,

Robinet²,

Meuleman³

et al. 2013

Front. Microbiol.

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“…HIV remains mainly subclinical in chimpanzees, although lymphadenopathy or weight loss is occasionally observed (Trimble et al 2000). HCV is mostly subclinical, and can be cleared by chimpanzees after acute infection, but can also progress to chronic hepatitis or liver disease (Bailey 2010). Based on clinical examinations and blood work performed at previous immobilizations (unpublished data), combined with continuous observation, none of the chimpanzees showed evidence of clinical disease.…”

Section: Animalsmentioning

confidence: 99%

Chemical immobilization of chimpanzees (Pan troglodytes) using a combination of detomidine and ketamine

Melis

Schauvliege

Bolhuis³

et al. 2012

Veterinary Anaesthesia and Analgesia

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“…A HCV-related hepacivirus of unknown origin, termed GBV-B, has been used as a surrogate model for HCV infection involving New World monkeys, where it causes hepatitis upon experimental inoculation [20,21]. The use of a surrogate model based on a related virus indicates a way to study HCV pathogenesis and immunity, even though neither monkeys nor apes are acceptable laboratory models in terms of accessibility and ethics [12,13,22]. Non-Primate hepaciviruses related to HCV have also been detected in dogs and horses [23,24].…”

Section: Introductionmentioning

confidence: 99%

Evidence for Novel Hepaciviruses in Rodents

et al. 2013

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Hepatitis C virus (HCV) is among the most relevant causes of liver cirrhosis and hepatocellular carcinoma. Research is complicated by a lack of accessible small animal models. The systematic investigation of viruses of small mammals could guide efforts to establish such models, while providing insight into viral evolutionary biology. We have assembled the so-far largest collection of small-mammal samples from around the world, qualified to be screened for bloodborne viruses, including sera and organs from 4,770 rodents (41 species); and sera from 2,939 bats (51 species). Three highly divergent rodent hepacivirus clades were detected in 27 (1.8%) of 1,465 European bank voles (Myodes glareolus) and 10 (1.9%) of 518 South African four-striped mice (Rhabdomys pumilio). Bats showed anti-HCV immunoblot reactivities but no virus detection, although the genetic relatedness suggested by the serologic results should have enabled RNA detection using the broadly reactive PCR assays developed for this study. 210 horses and 858 cats and dogs were tested, yielding further horse-associated hepaciviruses but none in dogs or cats. The rodent viruses were equidistant to HCV, exceeding by far the diversity of HCV and the canine/equine hepaciviruses taken together. Five full genomes were sequenced, representing all viral lineages. Salient genome features and distance criteria supported classification of all viruses as hepaciviruses. Quantitative RT-PCR, RNA in-situ hybridisation, and histopathology suggested hepatic tropism with liver inflammation resembling hepatitis C. Recombinant serology for two distinct hepacivirus lineages in 97 bank voles identified seroprevalence rates of 8.3 and 12.4%, respectively. Antibodies in bank vole sera neither cross-reacted with HCV, nor the heterologous bank vole hepacivirus. Co-occurrence of RNA and antibodies was found in 3 of 57 PCR-positive bank vole sera (5.3%). Our data enable new hypotheses regarding HCV evolution and encourage efforts to develop rodent surrogate models for HCV.

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An Assessment of the Use of Chimpanzees in Hepatitis C Research Past, Present and Future: 1. Validity of the Chimpanzee Model

Cited by 14 publications

References 309 publications

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Hepatitis C virus infection and related liver disease: the quest for the best animal model

Chemical immobilization of chimpanzees (Pan troglodytes) using a combination of detomidine and ketamine

Evidence for Novel Hepaciviruses in Rodents

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