Herpesviruses have developed strategies to counteract host defenses so as to allow viruses to infect cells and result in a latent or persistent infection. The goal of this project is to identify and determine the function of herpesvirus proteins that interact with host cell proteins to influence the course of infection. These proteins may allow us to identify new molecules that are important in the human immune system.Programmed cell death (apoptosis) is an antiviral defense mechanism used by the host to eliminate virus-infected cells. Some viruses encode proteins that interfere with signaling pathways for apoptosis. We have identified a protein encoded by a DNA virus, that inhibits programmed cell death. This virus, murine herpesvirus 68, shares several properties with the human Epstein-Barr virus. The M11 protein of murine herpesvirus 68 is homologous to a cellular protein, bcl-2, that is also known to inhibit programmed cell death. We have shown that the M11 protein inhibits programmed cell death induced by tumor necrosis factor and by the fas protein. In addition, we have also identified a domain within the viral protein that is required for inhibition of cell death.Interleukin-17 is a cytokine present in the human and mouse genomes that is also encoded by a monkey herpesvirus (herpesvirus saimiri). This virus naturally infects squirrel monkeys, but causes lymphomas in tamarins and can transform human T lymphocytes. We have found that when IL-17 is expressed by a virus, IL-17 enhanced the virulence of the virus and increased the replication of the virus in certain tissues. IL-17 inhibited the activity of natural killer cells, but did not affect the activity of cytotoxic T cells. IL-17 inhibited expression of another cytokine-interferon-alpha. IL-17 also altered the pattern of virus-specific antibody production. Taken together, these results suggest that IL-17 may allow the virus to modulate the immune system so that it can persist in animals despite an immune response.