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Peromyscus as a model system for human hepatitis C: An opportunity to advance our understanding of a complex host
Kurt J Vandegrift1, Justin T Critchlow1, Amit Kapoor2
1Department of Biology, The Pennsylvania State University, University Park, PA 16802, United States; Center for Infectious Disease Dynamics, The Pennsylvania State University, University Park, PA 16802, United States.
Abstract:
Worldwide, there are 185 million people infected with hepatitis C virus and approximately 350,000 people die each year from hepatitis C associated liver diseases. Human hepatitis C research has been hampered by the lack of an appropriate in vivo model system. Most of the in vivo research has been conducted on chimpanzees, which is complicated by ethical concerns, small sample sizes, high costs, and genetic heterogeneity. The house mouse system has led to greater understanding of a wide variety of human pathogens, but it is unreasonable to expect Mus musculus to be a good model system for every human pathogen. Alternative animal models can be developed in these cases. Ferrets (influenza), cotton rats (human respiratory virus), and woodchucks (hepatitis B) are all alternative models that have led to a greater understanding of human pathogens. Rodent models are tractable, genetically amenable and inbred and outbred strains can provide homogeneity in results. Recently, a rodent homolog of hepatitis C was discovered and isolated from the liver of a Peromyscus maniculatus. This represents the first small mammal (mouse) model system for human hepatitis C and it offers great potential to contribute to our understanding and ultimately aid in our efforts to combat this serious public health concern. Peromyscus are available commercially and can be used to inform questions about the origin, transmission, persistence, pathology, and rational treatment of hepatitis C. Here, we provide a disease ecologist's overview of this new virus and some suggestions for useful future experiments.
Insights
A new rodent model, Peromyscus maniculatus, offers a breakthrough for hepatitis C virus (HCV) research. This small mammal model overcomes limitations of previous systems, aiding the fight against hepatitis C infection and liver disease.
Area of Science:
- Virology
- Infectious Diseases
- Animal Models
Background:
- Hepatitis C virus (HCV) infects 185 million globally, causing 350,000 deaths annually.
- Human HCV research is limited by the lack of suitable in vivo models, with chimpanzee studies facing ethical and logistical challenges.
- Existing mouse models are insufficient for all human pathogens, necessitating alternative animal systems.
Purpose of the Study:
- To introduce a novel small mammal model for hepatitis C virus research.
- To highlight the potential of Peromyscus maniculatus as a tractable and genetically amenable model.
- To suggest future research directions for understanding HCV origin, transmission, pathology, and treatment.
Main Methods:
- Discovery and isolation of a rodent homolog of hepatitis C virus from Peromyscus maniculatus.
- Review of alternative animal models in pathogen research (ferrets, cotton rats, woodchucks).
- Discussion of the characteristics of rodent models, including tractability and genetic amenability.
Main Results:
- Identification of the first small mammal (mouse) model for human hepatitis C.
- Peromyscus maniculatus offers a viable alternative to non-human primate models.
- The model is commercially available, facilitating research accessibility.
Conclusions:
- The Peromyscus maniculatus model holds significant potential for advancing hepatitis C virus research.
- This model can address critical questions regarding HCV pathogenesis and inform treatment strategies.
- Further investigation using this model is crucial for combating the global public health threat of hepatitis C.
