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, SARS-CoV-2 (COVID-19), 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, SARS-CoV-2, 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, SARS-CoV-2, and MERS-CoV cause the most significant diseases of any of the human coronaviruses. The diseases are especially severe in aged populations. We are using mice infected with murine adapted strains of SARS-CoV and SARS-CoV-2 to understand the basis of these severe diseases. We also study the coronavirus that causes the Middle East Respiratory Syndrome (MERS-CoV). We have developed mouse models for studying MERS and 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 and from China. We have developed several mouse models for COVID-19 We are studying anosima, commonly found in COVID-19 patients and survivors.