HSV encoded viral functions

HSV编码的病毒功能

• 批准号: 8031043
• 负责人: BIN HE
• 金额: $ 22.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-15 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8031043
• 关键词: Affect; Antigen Presentation; Antiviral Agents; Attenuated; Blindness; CD4 Positive T Lymphocytes; CD80 gene; Cell Communication; Cell Maturation; Cell physiology; Cells; Coculture Techniques; Complex; Coupled; DNA Viruses; Dendritic Cells; Development; Disease; Elements; Encephalitis; Genes; Growth; HIV; Herpesvirus 1; Human; Human Herpesvirus 2; Immune system; In Vitro; Infection; Inflammatory; Interferon Type I; Interferon Type II; Interferons; Interleukin-12; Interleukin-6; Keratitis; Knowledge; Life Cycle Stages; Link; MHC Class II Genes; Natural Immunity; Nature; Oncolytic; Outcome; Pathway interactions; Process; Production; Recombinants; Research; Retroviridae; Risk Factors; Role; Sentinel; Series; Signal Pathway; Simplexvirus; System; T-Cell Activation; T-Lymphocyte; TANK-binding kinase 1; TNF gene; TNF receptor-associated factor 3; TNFRSF5 gene; Testing; Therapeutic; Toll-like receptors; Vaccines; Variant; Viral; Viral Antigens; Viral Pathogenesis; Viral Physiology; Viral Proteins; Virulence; Virulence Factors; Virus; Virus Diseases; Virus Replication; adaptive immunity; base; cytokine; cytosolic receptor; design; gene function; genital herpes; human IRF3 protein; immune function; in vivo; insight; interferon regulatory factor-3; mutant; novel; novel vaccines; pathogen; protein complex; transcription factor; transmission process

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.

描述（由申请人提供）：单纯疱疹病毒（HSV）建立持续感染，该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和发病机理结果的关键步骤。作为哨兵，树突状细胞桥接了先天和适应性免疫。有充分的文献证明，在感染后，未成熟的树突状细胞服用病毒抗原，经历成熟。在此过程中，联合刺激分子（例如MHC II类，CD40，CD80和CD86）被上调。此外，成熟的树突状细胞释放了炎症细胞因子，例如IL-6，IL-12，TNF-？和I型干扰素。这些细胞因子与树突状细胞协调以控制病毒感染。然而，HSV复制损害了树突状细胞功能。目前，由于HSV生命周期的复杂性质，对基本机制知之甚少。这项研究的目的是了解HSV？134.5调节树突状细胞成熟和功能的病毒机制。据认为，这种病毒因子会导致树突状细胞中类似Toll样的与先天信号通路的一种或多种细胞成分，并损害HSV感染中随后的T细胞激活。因此，将采用多面方法研究病毒和细胞元素的作用。将进行系统分析以在病毒复制和诱导共刺激分子和细胞因子的背景下定义关键功能域。此外，将进行研究以检查与病毒发病机理相关的HSV和树突状细胞相互作用的成分和性质。总之，这些研究不仅会提高我们对病毒感染机制的理解，而且还可以深入了解病毒感染中的树突状细胞功能。 公共卫生相关性：单纯疱疹病毒是引起诸如生殖器疱疹，角膜炎，失明和脑炎等疾病的人类病原体。单纯疱疹病毒感染也是艾滋病毒传播的危险因素。这项研究旨在研究单纯疱疹病毒如何损害限制病毒感染的免疫细胞功能。拟议的研究可能促进新型疫苗和抗病毒疗法的开发。