Research

Our research focuses on immune responses to viral infections in the central nervous system (CNS), with an emphasis on persistent infections and immune-mediated pathology. The disease model comprises a neurotropic coronavirus infection leading to encephalitis and a demyelinating disease resembling multiple sclerosis (MS). Our goal is to develop strategies to offset neurological and autoimmune disorders associated with acute and persistent CNS infections.

Our research has shown that multiple arms of the innate and adaptive immune response join forces to control virus replication in the CNS, yet virus persists at low levels in the presence of antiviral lymphocytes.

We are presently dissecting how distinct antiviral functions mediated by interferons and lytic T-cell mechanisms affect demyelination and viral replication in specific glial cell types. With respect to innate responses we are investigating how activation and function of antiviral factors in glial cells, specifically the OAS/RNaseL and PKR pathways alter viral tropism and disease outcome. Characterization of antigen presentation capacities as well as expression of activating and inhibitory ligands by glial cells will elucidate why T cells are initially effective, but become downregulated when infection persists. Lastly, the contributions of neutrophils and infiltrating monocytes to enhancing T cell entry and pathology are studied using selective knockout strategies.

A separate project related to viral persistence studies signals that maintain CNS lymphocytes and antibody secretion, which are common hallmarks of encephalitic infections and MS. Intrathecal antibody-secreting cells are critical to prevent virus re-emergence during the persistent phase of infection. Various transgenic and knockout mice are used to characterize the kinetics of B-cell differentiation and trafficking, as well as chemokines and B-cell survival factors regulating this process.