Innate Immune Responses and Vaccines Against Tumor-Associated Herpesviruses

描述（由申请人提供）：通过与宿主的共同进化，疱疹病毒获得了利用其宿主的策略，允许其自身终身持续存在，同时间歇性地分泌并传播给幼稚宿主。 通过逃避宿主的防御机制，疱疹病毒可以在宿主体内持续存在并引起各种疾病。γ-疱疹病毒亚科的成员（Epsetin-Barr病毒、卡波西肉瘤相关疱疹病毒和γ-疱疹病毒-68）在淋巴细胞中建立潜伏感染并在感染宿主中引起良性或恶性肿瘤的能力上是不同的。γ-疱疹病毒在急性和持续感染期间如何逃避宿主的先天免疫仍然是一个谜。了解病毒逃逸机制对于开发预防或控制病毒相关癌症的方法至关重要。先天免疫不仅是抵抗病原体的第一道防线，而且对于刺激适应性免疫应答也至关重要。目的是了解细胞启动先天性防御反应和肿瘤相关疱疹病毒阻碍防御机制的机制，为合理设计能够引起有效免疫反应并降低相关癌症发病率的候选疫苗奠定基础。有四个项目：1）γ-疱疹病毒与NLR的相互作用（Cart Ware）; 2）对γ-疱疹病毒感染的先天免疫应答的调节剂（Sumit Chanda）; 3）microRNA在调节宿主相互作用中的作用（Tariq Rana）; 4）恢复对γ-疱疹病毒的免疫应答（Ren Sun）;由管理核心（Ren Sun）协调，并由病毒学技术服务核心（Ting-Ting Wu）促进。一个具有不同和互补专业知识的调查小组一直在共同努力，并获得了关键的初步数据，作为该计划的基础。对病毒-宿主先天防御之间相互作用的分子和细胞机制的理解将用于开发新的疫苗策略。这项转化研究计划将为疫苗开发提供关键信息，以预防与γ-疱疹病毒相关的癌症。

DESCRIPTION (provided by applicant): Through co-evolution with hosts, herpesviruses have acquired strategies to exploit their hosts, allowing their own life-long persistence while intermittently being secreted and transmitted to naive hosts. By evading host defense mechanisms, herpesviruses can persist in hosts and cause various diseases. Members of the gamma-herpesvirus subfamily (Epsetin-Barr virus, Kaposi's sarcoma-associated herpesviruses and gamma herpesvirus-68) are distinct in their ability to establish latent infections in lymphocytes and cause benign or malignant tumors in infected hosts. It remains elusive how gamma-herpesviruses evade host innate immunity during their acute and persistent infections. Understanding the mechanisms of viral evasion mechanism is essential for developing approaches to prevent or control the virus associated cancers. Innate immunity is not only the first line of defense against pathogens, but is also critical for stimulating adaptive immune responses. The objective is to understand the mechanisms by which cells mount innate defense responses and tumor-associated-herpesviruses thwart components of the defense mechanisms, to establish a foundation for rational design of vaccine candidates that can elicit effective immune responses and reduce associated cancer incidence. There are four projects: 1) Interactions of gamma-herpesviruses with NLRs (Cart Ware); 2) Regulators of innate immune responses to gamma-herpesvirus infection (Sumit Chanda); 3) Role of microRNAs in regulating host interactions (Tariq Rana); 4) Restoring immune responses to gamma-herpesviruses (Ren Sun); coordinated by an Administrative Core (Ren Sun) and facilitated by a Virology Technical Service Core (Ting-Ting Wu). A team of investigators with diverse and complementing expertise has been working together and obtained critical preliminary data as the foundation for the Program. The understanding of the molecular and cellular mechanisms underlying the interactions between virus-host innate defenses will be utilized to develop a new vaccine strategy. This translational research program will provide critical information for vaccine development to prevent cancers associated with gamma-herpesviruses.