Licensure and Certifications

Education/Training Program Affiliations

Biosciences Graduate ProgramDepartment of Microbiology Graduate ProgramInterdisciplinary Graduate Program in ImmunologyInterdisciplinary Graduate Program in NeuroscienceInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program

Research Summary

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, 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 also identified mutations in a subdominant epitope that enhance immune recognition by CD8 T cells (heteroclitic epitopes) and are studying the structural basis of heteroclitic effects. We have developed a reverse genetics system for introducing these and other mutations into the murine coronavirus genome. 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 destruction.

The SARS-coronavirus causes the most significant disease of any of the human coronaviruses. The disease is especially severe in aged populations. We are using mice infected with murine adapted strains to understand the basis of this severe disease. We are also developing vaccines that might be useful if SARS were to recur, or more likely, as a model approach if another severe disease caused by a coronavirus were to emerge in human populations. We have begun studies of the coronavirus that causes the Middle East Respiratory Syndrome (MERS-CoV). We have developed a mouse model for studying MERS and begun to evaluate several MERS-CoV specific vaccines and therapies.

Perlman S,
Jacobsen G,
Olson A,
Afifi A.
Identification of the spinal cord as a major site of persistence during chronic infection with a murine coronavirus.
Virology.
1990 April. 175(2):418-26.
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