Animal Models Used in Hepatitis C Virus Research

Abstract

The narrow range of species permissive to infection by hepatitis C virus (HCV) presents a unique challenge to the development of useful animal models for studying HCV, as well as host immune responses and development of chronic infection and disease. Following earlier studies in chimpanzees, several unique approaches have been pursued to develop useful animal models for research while avoiding the important ethical concerns and costs inherent in research with chimpanzees. Genetically related hepatotropic viruses that infect animals are being used as surrogates for HCV in research studies; chimeras of these surrogate viruses harboring specific regions of the HCV genome are being developed to improve their utility for vaccine testing. Concurrently, genetically humanized mice are being developed and continually advanced using human factors known to be involved in virus entry and replication. Further, xenotransplantation of human hepatocytes into mice allows for the direct study of HCV infection in human liver tissue in a small animal model. The current advances in each of these approaches are discussed in the present review.

Structure-Based and Rational Design of a Hepatitis C Virus Vaccine

“…Finally, complete and consistent evaluations of vaccine designs may be impractical without overcoming current limitations in animal models and assessments of immunogenicity, including the lack of available immunocompetent animal models for HCV challenge studies, and the use of murine and guinea pig models in immunogenicity studies, as these species are unable to reflect key features of human bnAb responses to HCV [ 80 , 161 ] due to differences in antibody germline genes. Several of these limitations have been addressed by recent work, including the finding that E1E2 immunization in rhesus macaques can generate bnAbs with sequence and structural features that are similar to human bnAbs [ 162 , 163 ], and the identification and use of hepaciviruses as HCV surrogates for immunocompetent in vivo studies [ 164 , 165 ]. The many recent advances in HCV immunogen design and vaccine assessment, along with lessons and concepts from vaccine design efforts for other viruses and pathogens, can enable the successful development of an optimal and effective HCV vaccine.…”

The Status and Prospects of Epstein–Barr Virus Prophylactic Vaccine Development

“…Animal models are necessary and critical for the evaluation of infection or protection status against infectious disease pathogens and developing therapeutic drugs or vaccines. During the evaluation of vaccines against most pathogens, challenge experiments in animal models are considered the gold standard for the final assessment of vaccine efficacy (137)(138)(139)(140)(141). However, due to the restricted host tropism of EBV, a human herpesvirus, there is a limited range of susceptible candidate animal models (142-144) (Figure 3).…”

Bioengineered Liver Cell Models of Hepatotropic Infections

“…Chimpanzees have been used as an immunocompetent host when studying HBV and HCV infection and when evaluating novel immunotherapeutic approaches (reviewed by Wieland 2015) [19,20]. Furthermore, initial studies describing Pv liver stages were performed on either human or chimpanzee liver biopsies [21,22], and it was in chimpanzee models that the existence of small, non-replicating forms, the hypnozoites, was first reported [21].…”