Down regulation of MHC class I cell surface expression in Marek's disease virus (MDV) infection and its relevance in vivo

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Marek's disease virus (MDV) causes a devastating T cell tumor in the chicken. Down regulation of cell surface MHC class I expression is a hallmark of lytic MDV infection. Our goal is to gain a complete understanding of the significance of MHC class I down regulation in the pathogenesis of alphaherpesvirus-induced disease. The proposed studies focus on the role of virus interference with MHC class I with regard to virus delivery to the site of free virus production in the skin, the establishment of latent infection in T celts, and tumor formation. Our hypothesis is that sustained down regulation of MHC class I on the surface of infected cells by (a) viral gene product(s) expressed during the lytic replication cycle facilitates virus survival, spread within and between animals, and the establishment of latent infection by allowing an escape from the action of cytotoxic T lymphocytes (CTL). The hypothesis is tested by specific aims that will first focus on further proof of MHC class I down regulation in vitro induced by candidate proteins. Secondly, cellular partners of the viral proteins will be identified and mechanism(s) of virus-specific MHC class I down regulation determined. Finally and importantly, the relevance of the virus-induced block in MHC class I antigen presentation on virus replication in vivo and pathogenesis will be determined.