HSV encoded viral functions

描述(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。尽管参与的因素很多，但越来越多的证据表明，单纯疱疹病毒与树突状细胞的相互作用是决定病毒感染结局和发病机制的关键步骤。作为哨兵，树突状细胞在先天免疫和获得性免疫之间架起桥梁。研究表明，未成熟的树突状细胞在感染病毒后，会结合病毒抗原，经历成熟过程。在这个过程中，共刺激分子如MHC II类分子、CD40、CD80和CD86被上调。此外，成熟的树突状细胞还会释放炎性细胞因子，如IL-6、IL-12、TNF-β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，单纯疱疹病毒复制损害了树突状细胞的功能。目前，由于HSV生命周期的复杂性，人们对其潜在的机制知之甚少。本研究的目的是了解单纯疱疹病毒134.5调节树突状细胞成熟和功能的病毒机制。据认为，这种病毒因子扰乱了树突状细胞中与Toll样相关的天然信号通路的一个或多个细胞成分，并损害了HSV感染后T细胞的激活。因此，将采取多方面的方法来研究病毒和细胞成分的作用。将进行系统分析，以确定病毒复制和共刺激分子和细胞因子诱导的关键功能区域。此外，还将进行研究，以检查与病毒致病相关的单纯疱疹病毒和树突状细胞相互作用的成分和性质。综上所述，这些研究不仅将促进我们对病毒感染机制的理解，还将为深入了解树突状细胞在病毒感染中的功能提供帮助。 公共卫生相关性：单纯疱疹病毒是人类病原体，可导致生殖器疱疹、角膜炎、失明和脑炎等疾病。单纯疱疹病毒感染也是艾滋病毒传播的风险因素。这项研究旨在调查单纯疱疹病毒如何损害限制病毒感染的免疫细胞的功能。拟议的研究可能会促进新型疫苗和抗病毒疗法的开发。

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.