Regulation of viral latency in gamma-herpesvirus infection

疱疹病毒感染给公共卫生带来的代价是巨大的。伽玛疱疹病毒慢性感染着世界上95%以上的人口。这组病毒引起一种免疫抑制状态，导致免疫反应下调。这使得病毒有机会逃避免疫系统，从而在宿主体内存活。伽玛疱疹病毒通常不会导致正常个体的严重疾病，但在免疫系统不成熟或受损的个人中，伽马疱疹病毒的重新激活可能会导致严重疾病，甚至死亡。病毒重新激活是免疫抑制疾病的主要并发症，如艾滋病毒(目前影响着4500多万人)和移植接受者。病毒诱导的宿主细胞变化可导致继发感染、移植后淋巴增生性疾病，甚至肿瘤的发展。这项建议中描述的研究的中心目的是了解调节病毒如何在宿主中维持的细胞和病毒机制。这些研究将提高我们对抗原提呈细胞和CD8+T淋巴细胞如何确保维持免疫反应的理解，并可能识别关键靶点，以促进抗病毒药物和疫苗的合理设计。

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.