HSV encoded viral functions

描述（由申请人提供）：单纯疱疹病毒（HSV）建立持续感染，病毒以复杂的方式调节宿主免疫系统。尽管涉及许多因素，但新出现的证据表明，HSV和树突状细胞的相互作用是决定病毒感染结果和发病机制的关键步骤。树突状细胞作为哨兵，架起先天免疫和适应性免疫的桥梁。有充分的证据表明，在感染时，未成熟的树突状细胞吸收病毒抗原，经历成熟。在此过程中，MHC II类、CD40、CD80、CD86等共刺激分子上调。此外，成熟树突状细胞释放炎性细胞因子，如IL-6、IL-12、TNF-？和I型干扰素。这些细胞因子与树突状细胞协同控制病毒感染。然而，HSV的复制损害了树突细胞的功能。目前，由于HSV生命周期的复杂性，对其潜在机制知之甚少。本研究的目的是了解HSV 134.5调节树突状细胞成熟和功能的病毒机制。据信，这种病毒因子干扰树突状细胞中toll样相关先天信号通路的一种或多种细胞组分，并损害HSV感染中随后的T细胞激活。因此，将采取多方面的方法来研究病毒和细胞因素的作用。将进行系统分析，以确定在病毒复制和诱导共刺激分子和细胞因子的背景下的关键功能域。此外，研究将进行检查成分和性质的HSV和树突状细胞相互作用相关的病毒发病机制。总之，这些研究不仅将促进我们对病毒感染机制的理解，而且还将提供对病毒感染中树突状细胞功能的深入了解。

DESCRIPTION (provided by applicant): Herpes simplex viruses (HSV) establish persistent infections where the viruses modulate host immune systems in a complex way. Although many factors are involved, emerging evidence indicates that the interaction of HSV and dendritic cells is a key step which dictates the outcome of viral infection and pathogenesis. As sentinels, dendritic cells bridges innate and adaptive immunity. It is well documented that upon infection immature dendritic cells take up viral antigens, undergo maturation. In this process, co-stimulatory molecules such as MHC class II, CD40, CD80, and CD86 are up-regulated. Additionally, mature dendritic cells release inflammatory cytokines such as IL-6, IL-12, TNF-?, and type I interferon. These cellular factors coordinate with dendritic cells to control viral infection. Nevertheless, HSV replication compromises dendritic cell functions. Currently, little is known about underlying mechanisms due to the complex nature of HSV life cycles. The objective of this research is to understand the viral mechanisms through which HSV ?134.5 modulate dendritic cell maturation and functions. It is believed that this viral factor perturbs one or more of cellular components of Toll-like related innate signaling pathways in dendritic cells and impairs subsequent T cell activation in HSV infection. As such, multi-faceted approaches will be taken to investigate the roles of viral and cellular elements. Systematic analysis will be carried out to define critical functional domains in the context of viral replication and the induction of co-stimulatory molecules and cytokines. Additionally, studies will be performed to examine components and the nature of HSV and dendritic cell interactions relevant to viral pathogenesis. Together, these studies will not only advance our understanding of the mechanisms of viral infection but also provide an insight into dendritic cell functions in viral infections. PUBLIC HEALTH RELEVANCE: Herpes simplex viruses are human pathogens that cause diseases such as genital herpes, keratitis, blindness, and encephalitis. Herpes simplex virus infection is also a risk factor in HIV transmission. This research is designed to investigate how herpes simplex viruses impair the functions of immune cells which restrict viral infections. The proposed research may facilitate the development of novel vaccines and antiviral therapeutics.