Regulation of viral latency in gamma-herpesvirus infection

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The cost to public health from herpesvirus infection is enormous. The gamma-herpesviruses chronically infect more than 95% of the world's population. This group of viruses induce a state of immunosuppression that cause down-regulation of immune responses. This allows the virus the opportunity to evade the immune system and thus survive within the host. The gamma-herpesviruses do not generally cause serious disease in normal individuals but reactivation of gamma-herpesviruses can cause severe disease, even mortality, in individuals with an immature or a compromised immune system. Viral reactivation is a major complication of immunosuppressive diseases such as HIV (which currently affects more than 45 million people) and in transplant recipients. The virally-induced changes in the host cells can result in the development of secondary infections, post-transplantation lymphoproliferative disease and even the development of tumours. The central aim of the studies described in this proposal is to understand the cellular and viral mechanisms regulating how the virus is maintained in the host. These studies will improve our understanding of how antigen presenting cells and CD8+ T lymphocytes ensure an immune response is maintained and may identify critical targets to facilitate the rational design of antiviral drugs and vaccines.