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Animal Models of Hepatitis C Virus Infection
Alexander Ploss1, Amit Kapoor2
1Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.
Insights
Developing effective Hepatitis C virus (HCV) vaccines and treatments requires better animal models. Researchers are exploring humanized mice and related hepaciviruses, like RHV-rn1 in rats, to study HCV infection and immune responses.
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) chronically infects approximately 71 million people globally.
- HCV's limited host range (humans and chimpanzees) complicates in vivo research and vaccine development.
- Ethical and practical limitations of chimpanzee research necessitate alternative animal models.
Purpose of the Study:
- To review current strategies for creating small animal models for Hepatitis C virus infection.
- To assess the progress and limitations of existing humanized mouse models.
- To explore alternative approaches, including virus adaptation and related hepaciviruses, for studying HCV immunopathogenesis and vaccine development.
Main Methods:
- Review of various approaches to develop small animal models for HCV.
- Evaluation of humanized mouse models for HCV infection.
- Investigation of virus adaptation strategies and related hepaciviruses (e.g., RHV-rn1).
Main Results:
- Humanized mouse models show progress but do not fully replicate immunocompetent HCV infection.
- Rodent/rat hepacivirus (RHV-rn1) in immunocompetent rats shows promise as a surrogate model.
- Further characterization of these models is needed to understand HCV immunopathogenesis and inform vaccine design.
Conclusions:
- Small animal models are crucial for advancing HCV research and vaccine development.
- Humanized mice and RHV-rn1 in rats represent promising but incomplete solutions.
- Continued research and characterization of novel animal models are essential for understanding HCV and creating effective vaccines.
Abstract:
Hepatitis C virus (HCV) is an important and underreported infectious disease, causing chronic infection in ∼71 million people worldwide. The limited host range of HCV, which robustly infects only humans and chimpanzees, has made studying this virus in vivo challenging and hampered the development of a desperately needed vaccine. The restrictions and ethical concerns surrounding biomedical research in chimpanzees has made the search for an animal model all the more important. In this review, we discuss different approaches that are being pursued toward creating small animal models for HCV infection. Although efforts to use a nonhuman primate species besides chimpanzees have proven challenging, important advances have been achieved in a variety of humanized mouse models. However, such models still fall short of the overarching goal to have an immunocompetent, inheritably susceptible in vivo platform in which the immunopathology of HCV could be studied and putative vaccines development. Alternatives to overcome this include virus adaptation, such as murine-tropic HCV strains, or the use of related hepaciviruses, of which many have been recently identified. Of the latter, the rodent/rat hepacivirus from Rattus norvegicus species-1 (RHV-rn1) holds promise as a surrogate virus in fully immunocompetent rats that can inform our understanding of the interaction between the immune response and viral outcomes (i.e., clearance vs. persistence). However, further characterization of these animal models is necessary before their use for gaining new insights into the immunopathogenesis of HCV and for conceptualizing HCV vaccines.
