What are the immune correlates of protection against HCV persistence? Can immunity conferred by natural virus clearance or vaccination protect against heterologous viruses? We isolated several strains of HCV-like viruses from feral rats, developed a reverse genetic system for rat hepacivirus and now we’re using these genetically diverse variants to study the nature and breadth of immunity conferred by vaccination or spontaneous virus clearance in laboratory rats and mice. To test vaccine efficacy, we are using laboratory rats, since they are the natural host of these viruses and are therefore fully susceptible to HCV-like lifelong viral persistence seen in humans. Parallel studies in mice are used to accurately define the role of host factors in viral immunity and pathogenesis. We expect our studies will inform the research and development of HCV vaccines for humans.
How do different liver cells respond to HCV infection? What transcriptome changes presage different infection outcomes? What is the origin of liver inflammation during chronic HCV infection? We are optimizing approaches to disintegrate liver into constituent cells, while preserving their transcriptomes for RNA-seq analysis.
GBV-C or Human Pegivirus is a common human infection. The virus is genetically related to HCV and belongs to the family Falviviridae. In developed countries, 1-5%, and in developing countries, up to 20% of healthy blood donors were found positive for GBV-C viremia. GBV-C can establish persistent infection, more commonly in HIV or HCV infected individuals. Similarly, Torque-teno viruses are small-circular DNA viruses that commonly infect humans and are more prevalent in blood transfusion recipients. Both these viruses are common components of human blood virome, are strictly species specific, and thus lack animal models. We recently isolated homologs of these viruses from feral rodents to develop informative laboratory models. Our goal is to determine the health relevance of these viral infections and mechanisms underlying their persistence.
We are characterizing the viromes of feral and wild rodents. Our recent published work describes many new animal viruses, including the first identification of animal HCV-like viruses. More recently, we identified a new parvovirus associated with Theiler’s diseases in horses. We are also characterizing viromes in human clinical samples to understand how virome composition affects human health.