Stanley Perlman, M.D., Ph.D.
Ph.D., MIT, 1972; M.D., University of Miami, 1979 |
Professor of Microbiology Campus address: 3-712 BSB Mailing address: 51 Newton Rd. 3-712 Bowen Science Building Iowa City, IA 52242 Phone: 319-335-8549 Email: |
Study of virus induced demyelination
My laboratory has been interested in the pathogenesis of murine coronavirus infections for several years. Now, we will 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.
Perlman Lab Home Page
Recent publications
Trandem K, Zhao J, Perlman S. (2011) Highly activated cytotoxic CD8 T cells express protective IL-10 at the peak of viral encephalitis. J. Immunol. 186:3642-3652. PMCID: PMC3063297
Trandem K, Jin Q, Weiss K, James B, Zhao J, Perlman S. (2011). Virally expressed IL-10 ameliorates acute encephalomyelitis and chronic demyelination in coronavirus-infected mice. J. Virol. 85:6822-31. PMCID: PMC3126551
Zhao J, Zhao J, Fett C, Trandem K, Fleming F, Perlman S. (2011). IFN-γ and IL-10-expressing virus epitope-specific Foxp3+ Tregs in the central nervous system during encephalomyelitis. J. Exp. Med. 2011 Jul 11. [Epub ahead of print].
Zhao J, Zhao J, van Rooijen N, Perlman S. (2009) Evasion by stealth: Inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice. PLoS Pathogens, Oct;5(10):e1000636. Epub 2009 Oct 23. PMC2762542
Zhao J, Zhao J, Perlman S. (2009) De novo recruitment of antigen-experienced and naïve T cells contributes to the long term maintenance of anti-viral T cell populations in the persistently infected CNS, J. Immunol. 183:5163-5170. PMC2811315
Perlman S, Netland J. (2009) Coronaviruses post-SARS: Update on replication and pathogenesis, Nature Reviews Microbiology 7:439-450. PMC2830095