Human cytomegalovirus (HCMV) is a major human pathogen capable of establishing acute, persistent and latent infections. The role of specific viral gene products in these aspects of pathogenesis, however, is poorly understood. One viral proteins that is likely to be important to HCMV pathogenesis is the abundant, virion-associated phosphoprotein, pp65. However, the role of pp65 has proven difficult to ascertain because of the strict species specificity of HCMV, which precludes analysis of viral pathogenesis in an animal model system. To circumvent this problem, we propose to examine the Murine Cytomegalovirus homologue of the HCMV pp65 protein, M83. A recombinant virus will be constructed which contains a deletion in the M83 gene. The replicative properties of this mutant virus will be examined in tissue culture. In addition, the pathogenic properties of the M83 deletion mutant will be examined in mice by determining the ability of the virus to establish acute infection in major target organs, persistent infection in salivary glands, and latent infection in the spleen. This analysis will allow a determination of the role of the M83 protein in the major aspects of viral pathogenesis, and of the role of the HCMV pp65 protein in the progression of HCMV-associated illness.
