Dr. Jack Stapleton, Professor of Infectious Diseases, has just had his grant “Novel viral immune interference mechanisms: HCV as a model system” funded by a four-year, $650,000 VA Merit grant. Dr. Stapleton provided a detailed description of what specific avenues of research this will fund:
Viruses have evolved mechanisms to evade recognition by the immune system of their infected human host. Viruses with an RNA genome like Zika, Polio virus, Dengue, and Hepatitis C virus [HCV] have a variety of proteins that interfere with various steps in immune cell function. In our last VA Merit Review grant, we discovered a new mechanism used by two RNA viruses to evade recognition by the host. This mechanism utilizes the virus RNA genome molecule to reduce the production of an enzyme that is necessary for normal function of human T cells. Since T cell function is critical for almost all aspects of the human immune response, a small reduction in function may explain how these viruses are able to establish infection, and in the case of hepatitis C virus, persist for decades in humans. Furthermore, by altering the RNA molecule to no longer reduce the T cell enzyme, improved immune responses to viral vaccines may be possible.
In this grant, in collaboration with Dr. Warren Schmidt of the Liver Clinic, we will examine how these viruses direct their RNA genome to immune cells both in the laboratory, and in immune cells obtained from infected people. We will also study how this RNA regulation of cellular processes affects liver cells, and the immune response to viral vaccines. The ultimate goal is to use this information to develop potential viral therapies and vaccines.
This is a continuation of investigations Dr. Stapleton and members of his laboratory have made into HCV mechanisms. In an October 2015 interview, we had an opportunity to speak with Dr. Stapleton and then-Assistant Research Scientist Dr. Nirjal Bhattarai on their research and its implications for lower-cost potential therapeutics.
Congratulations to Dr. Stapleton on securing the funding to continue this important research.