Colorado Hepatitis C Cooperative Research Center

描述(由申请人提供)： 这份申请续签丙型肝炎合作研究中心(HCVCRC)的重点是丙型肝炎病毒用来逃避或抑制免疫反应的多细胞机制。来自以富有成效的方式密切合作的个人投资机构的三个高度相互关联的项目将描述影响自发解决或病毒持续发生的先天性免疫和获得性免疫的不同组成部分。该提案实现了本RFA所述的几个目标，包括但不限于：1.确定丙型肝炎病毒诱导的先天免疫信号的影响因素(项目1，目标3；项目3)；描述其在丙型肝炎病毒控制中的机制(项目1/目标1，目标3)；解释丙型肝炎病毒如何抑制先天免疫途径(项目1/目标1；项目3/目标3)。2.确定获得性免疫清除丙型肝炎病毒感染及其功能崩溃导致病毒持续存在的机制(项目1/AIMS 1和2；项目2/ALMS 1、2和3.阐明先天免疫和获得性免疫反应如何整合以实现丙型肝炎病毒感染的清除(项目1/AIMS 1.项目3/AIM 3)。该中心应用程序的首要目标是了解参与调节丙型肝炎病毒感染恢复的多细胞过程，以及为什么这些过程经常失败并导致病毒持续存在，并进一步确定将细胞从免疫衰竭和失败中拯救出来的目标。从我们的记录中可以明显看出，个别项目从他们参与这项丙型肝炎病毒研究报告中受益匪浅，因为每个研究人员都从截然不同但互补的研究领域带来了独特的专门知识和资源。这些学科包括临床肝病学、细胞和分子免疫学、病毒学、细胞生物学和系统生物学。

DESCRIPTION (provided by applicant): This application for renewal of a Hepatitis C Cooperative Research Center (HCV CRC) focuses on the multicellular mechanisms employed by HCV to evade or suppress the immune response. Three highly inter-related projects from PIs who have worked closely together in a productive manner will characterize diverse components of innate and adaptive immunity that influence whether spontaneous resolution or viral persistence occurs. The proposal fulfills several of the stated aims of this RFA, including but not limited to: 1. Identify effectors of HCV-induced innate immune signaling (project 1, aim 3; project 3); describe their mechanisms in HCV control (project 1/aim 1, aim 3); explain how HCV inhibits innate immune pathways (project 1/aim 1; project 3/aim3). 2. Determine the mechanisms of the adaptive immunity in clearance of HCV infection and their functional collapse leading to virus persistence (project 1/aims 1 and 2; project 2/ alms 1, 2, and 3. Clarify how the innate and adaptive immune responses are integrated to effect clearance of HCV infection (project 1/ aim 1 .project 3/ aim 3). The overarching objective of this Center application is to understand the multi-cellular processes involved in mediating recovery from HCV infection, and conversely, why these processes often fail and lead to viral persistence, and furthermore, identify targets to rescue cells from immune exhaustion and failure. As evident from our track record, the individual projects benefit significantly from their participation in this HCV CRC since each investigator brings unique expertise and resources from substantially different yet complementary areas of research. These include clinical hepatology, cellular and molecular immunology, virology, cell biology, and systems biology.