Effectors of demyelination in a murine coronavirus model of infection.

I am currently studying the role of complement components in antibody-mediated demyelinating disease in mice infected with Mouse Hepatitis Virus strain JHM (MHV-JHM). Immunocompetent mice infected with MHV-JHM develop demyelination whereas mice lacking the recombinase activation gene (RAG1), which lack T and B cells, succumb to encephalitis without demyelination. Our lab has determined that both CD4, CD8, and II T cells can mediate demyelination. Recently, we have observed demyelination in RAG1-/- mice treated with anti-MHV antibody. Demyelination in these mice was decreased significantly in RAG1-/- mice lacking activating Fcγ receptors I/III and in those depleted of complement with Cobra Venom Factor (CVF). Currently, I am investigating antibody-mediated demyelination in RAG1-/- mice deficient in components of the complement pathway, and in mice treated with antagonists to the complement receptors for C3a and C5a. Through creation of recombinant MHV viruses, I am also investigating whether production of complement components in infected cells is sufficient for induction of demyelination in the absence of other signals.

Templeton SP, Perlman S. Role of IFN-gamma responsiveness in CD8 T-cell-mediated viral clearance and demyelination in coronavirus-infected mice. J Neuroimmunol. 2008 Feb;194(1-2):18-26. Epub 2007 Dec 21. PubMed PMID: 18082272.

Templeton SP, Kim TS, O'Malley K, Perlman S. Maturation and localization of macrophages and microglia during infection with a neurotropic murine coronavirus. Brain Pathol. 2008 Jan;18(1):40-51. Epub 2007 Oct 12. PubMed PMID: 17935605.

Templeton SP, Perlman S. Pathogenesis of acute and chronic central nervous system infection with variants of mouse hepatitis virus, strain JHM. Immunol Res. 2007;39(1-3):160-72. Review. PubMed PMID: 17917063.