Innate Immune Responses and Vaccines Against Tumor-Associated Herpesviruses

描述(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，允许自己终身存在，同时间歇性地分泌并传播给幼稚的宿主。通过逃避宿主防御机制，疱疹病毒可以在宿主体内持续存在，并导致各种疾病。伽马疱疹病毒亚家族的成员(Epsetin-Barr病毒、卡波西肉瘤相关疱疹病毒和伽马疱疹病毒-68)在建立淋巴细胞潜伏感染和在受感染宿主中引起良恶性肿瘤方面具有独特的能力。伽马疱疹病毒在其急性和持续感染期间如何逃避宿主的先天免疫仍然难以捉摸。了解病毒逃逸机制对于开发预防或控制病毒相关肿瘤的方法至关重要。先天免疫不仅是抵御病原体的第一道防线，也是激发适应性免疫反应的关键。其目的是了解细胞启动天然防御反应和肿瘤相关疱疹病毒抑制防御机制的机制，为合理设计能够引发有效免疫反应和降低相关癌症发病率的候选疫苗奠定基础。有四个项目：1)伽马疱疹病毒与NLR的相互作用(CART Ware)；2)伽马疱疹病毒感染的先天免疫反应的调节(Sumit Chanda)；3)microRNAs在调节宿主相互作用中的作用(Tariq Rana)；4)恢复对伽马疱疹病毒的免疫反应(Ren Sun)；由行政核心(Ren Sun)协调和由病毒学技术服务核心(Ting-Ting Wu)促进。一个具有不同专业知识和互补专业知识的调查小组一直在合作，并获得了关键的初步数据，作为该计划的基础。对病毒-宿主天然防御之间相互作用的分子和细胞机制的理解将被用于开发新的疫苗策略。这一转化研究计划将为疫苗开发提供关键信息，以预防与伽马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.