Using mice to understand human hepatitis C

Peromyscus is an abundant and geographically widespread small mammal that is easily trapped and studied in the field. It is also bred and used in experiments in the laboratory, allowing researchers to utilize this species as a natural model to test hypotheses in both settings. Peromyscus can be used to evaluate multiple scales of epidemiological questions due to trap-ability (e.g. trapping grids can be set up at both the individual- and population- levels), and these grids can be replicated and manipulated differently. Further, Peromyscus carry numerous zoonotic pathogens and may be a reservoir or vector in certain locations. For these reasons, CIDD’s Kurt Vandegrift, Justin Critchlow, David Friedman, Peter Huson, and Amit Kapoor from Nationwide Children’s Hospital, use Peromyscus as a model for human hepatitis C epidemiology.

A hepatitis C homolog was recently discovered in Peromyscus and researchers hope to exploit the plasticity and utility of Peromyscus to study the dynamics of the virus. Hepatitis C virus (HCV) infects 185 million people and attributed to ~366,000 deaths annually worldwide. HCV is mainly transmitted by sharing blood, although up to 50% lack a clear transmission route. There is great viral diversity of HCV, making it difficult to test for antibodies and create vaccines, and helps the virus evade the immune system. A new type of treatment called DAA targets specific nonstructural proteins that prevent the virus from replicating. Even though these drugs have a ~90% clearance rate, they are expensive and reinfection is possible. Finally, much of the host-virus interaction within the liver is unknown because it requires study while the host is infected. Thus, HCV infected Peromyscus provide an opportunity for experimentation and learning about viral dynamics.

Vandegrift et al. claim Peromyscus models will elucidate HCV transmission, immunity, persistence, pathology, and treatment. Questions of interest include: What concentrations of virus are necessary for transmission? What are the mechanisms for vertical transmission? Which host immune system attributes or functions determine infection outcomes? How can researchers predict which patients will develop clinical symptoms? Overall, Peromyscus models provide an opportunity to test HCV hypotheses in the field and lab, which may lead to better understanding and treatment of human hepatitis C virus.

Synopsis written by Ellen Brandell

Picture from Patrick Mansell