The impact of interplays between viral immune evasion proteins and host cell-surface receptors on viral pathogenesis

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Herpesviruses can cause infections that persist for the lifetime of the individual. These viruses have evolved a range of mechanisms to evade the host's immune response that would otherwise eliminate them. One member of the herpesvirus family that is replete with methods for avoiding the immune response is cytomegalovirus. This virus, while not causing symptoms in healthy people, is a significant cause of disease and mortality in indivuals who are immunosuppressed such as AIDS patients or people undergoing transplantation, or in neonates who have poorly developed immune responses. In the current project we will explore how virally encoded proteins that bind to cell surface receptors expressed on a class of immune effector cell called the Natural Killer (NK) cell, can interfere with the functions of these cells. We will seek to define the NK cell proteins that are specifically bound by these viral proteins and also make deletion mutants of these viral genes to assess what effect knocking out these genes has on virus-caused disease. These studies will provide important insights into novel mechanisms of viral immune evasion and may provide insights into how therapies could be developed that interfere with the functions of these viral proteins.