Study of coronavirus pathogenesis, including demyelination, SARS and MERS
My laboratory examines the pathogenesis of murine coronavirus-induced demyelination and the respiratory infections caused by the human coronaviruses that caused the Severe Acute Respiratory Syndrome (SARS) and the Middle East Respiratory Syndrome.
Mice infected with mouse hepatitis virus develop a demyelinating disease with many similarities to the human disease, multiple sclerosis. Research in my laboratory is aimed at determining the immunological and viral factors involved in the demyelinating process. Previously, we determined the CD4 and CD8 T cell epitopes recognized in the central nervous system (CNS) of infected mice. We showed that in mice infected chronically with the virus, cytotoxic T cell escape mutants arise. These mutations completely abrogate recognition by CD8 T cells and thereby facilitate persistence. We have developed a reverse genetics system for introducing mutations into the murine coronavirus genome. We have developed a model to determine the role of individual effector molecules in demyelination, using immunodeficient mice infected with the virus. Most recently, we are interested in the role of regulatory T cells, including those that express IL-10 in the demyelinating process.
We developed several novel mouse models for SARS and MERS, and examine the role of the innate and adaptive immune responses in the development of the respiratory disease observed in these mice. We are most interested in why aged compared to young individuals are at much greater risk for severe disease.