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| Study of coronavirus pathogenesis, including demyelination and SARS | |||||||
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My laboratory examines the pathogenesis of murine coronavirus-induced demyelination and the respiratory infection caused by the human coronavirus that caused the Severe Acute Respiratory Syndrome (SARS).
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 examine the role of the innate and adaptive immune responses in the development of the respiratory disease observed in these mice. We are developing a vaccine that will be useful in any future outbreaks of SARS. |
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| Selected Publications | |||||||
| Click Here for a Complete List of Articles | |||||||
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Butler, N., Theodossis, A., Webb, A., Dunstone, M., Nastovska, R., Ramarathinam, S.R., Rossjohn, J., Purcell, A.W. and Perlman S. Structural and biological basis of CTL escape in coronavirus-infected mice. J. Immuno. 180:3926-3937, 2008.
Anghelina, D., Zhao, J., Trandem, K. and Perlman S. Role of regulatory T cells in coronavirus-induced acute encephalitis. Virology 385:358-365, 2009. Zhou, H. and Perlman S. Mouse hepatitis virus does not induce beta interferon synthesis and does not inhibit its induction by dsRNA. J. Virol. 81: 568-574, 2007. Netland, J., Meyerholz, D., Moore, S., Cassell, M. and Perlman S. SARS-CoV infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2 mice. J.Virol 82:7264-75, 2008. |
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| Department/Program Affiliations |
| Microbiology |
| Biosciences |
| Immunology |
| MSTP |
| Neuroscience |