Animal models for the study of hepatitis C virus infection and related liver disease

Area of Science:

• Hepatology
• Virology
• Immunology

Background:

• Hepatitis C virus (HCV) infection leads to significant annual liver-related mortality globally.
• Current treatments for chronic HCV remain suboptimal, necessitating further research.
• No effective vaccine currently exists to prevent HCV infection.

Purpose of the Study:

• To review the utility of animal models in Hepatitis C virus (HCV) research.
• To highlight the strengths and limitations of existing animal models for drug and vaccine development.

Main Methods:

• Review of current literature on animal models for HCV research.
• Comparative analysis of chimpanzee models and small animal models (T- and B-cell deficient mice with human chimeric livers).
• Discussion of recent advancements in genetically humanized mouse models.

Main Results:

• Chimpanzees serve as the optimal model for studying HCV infection and host immune responses, including vaccine immunogenicity and efficacy.
• T- and B-cell deficient mice with human chimeric livers are valuable for studying HCV neutralization, viral entry, innate immunity, and therapeutics, despite limitations in adaptive immunity studies.
• Genetically humanized mice show promise but currently allow only for the study of specific HCV life cycle steps with limited replication.

Conclusions:

• Animal models, particularly chimpanzees and humanized mice, are indispensable for advancing Hepatitis C virus (HCV) research.
• Continued development and refinement of these models are essential for the creation of effective HCV vaccines and therapies.