My laboratory has been interested in the pathogenesis of murine coronavirus infections for several years. Now, we also study three respiratory human coronavirus infections: SARS(Severe Acute Respiratory Syndrome)-coronavirus, Middle East Respiratory syndrome (MERS)-coronavirus, human coronavirus-OC43 and human coronavirus-NL63.
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 reverse genetics system for introducing mutations into the murine coronavirus, SARS-CoV and MERS-CoV genomes. We also study the anti-inflammatory components that are needed to diminish immunopathological disease, with specific focus on regulatory CD4 T cells and IL-10. The ultimate goal of our work is to understand the interplay of pro and anti-inflammatory factors that result in myelin and lung destruction.
SARS-CoV and MERS-CoV causes the most significant diseases of any of the human coronaviruses. The disease is especially severe in aged populations. We are using mice infected with murine adapted strains of SARS-CoV to understand the basis of this severe disease. We have begun studies of the coronavirus that causes the Middle East Respiratory Syndrome (MERS-CoV). We have developed mouse models for studying MERS and begun to evaluate several MERS-CoV specific vaccines and therapies. We also study immune responses in patients who survived MERS, in collaboration with investigators from the Kingdom of Saudi Arabia.
- T cell Biology
- Vaccines, Drugs, and Biologics