: Human cytomegalovirus (HCMV), a member of the beta-herpesvirus family, is a significant cause of morbidity, especially in those who are immunocompromised and in fetuses. It is well known that HCMV possesses several immune evasion genes, the glycoprotein products of which interfere with class I MHC restricted antigen presentation. These glycoproteins subvert the recognition and destruction of virally infected cells by the host's immune system, especially by CD8+ cytotoxic T cells (CTLs). We plan to use a transgenic murine model of HCMV infection in order to study HCMV's use of immunoevasins to subvert antigen processing and presentation. We will make a recombinant CMV (rCMV) which will contain HCMV immune evasion genes known to disrupt the presentation of antigens by class I MHC molecules. The mice will be deficient for H-2 Kb and H-2 Db while carrying a transgene for HLA-A2, the alpha-3 domain of which will be replaced by its murine counterpart to ensure proper development of murine CTLs. By infecting the transgenic mice with rCMV, we will be able to study how the CTL response is affected by HCMV immunoevasins in vivo. This may be the only way to explain the mechanisms that these genes use to evade the immune response in vivo.
