Modulation of innate immunity by HIV-1 gene products

描述（由申请人提供）：与HIV-1感染相关的免疫发病机制以免疫系统细胞群的几种功能异常和CD4+ T淋巴细胞数量和功能的进行性下降为特征。尽管作出了许多努力，但最终导致艾滋病发展的机制尚未完全阐明。本提案的总体目标是表征早期HIV相互作用以及HIV-1基因产物对先天免疫系统细胞群的旁观者效应，目的是确定与理解艾滋病免疫发病机制相关的病毒持久性和免疫系统功能障碍的新机制。根据免疫反应的功能结果可能由所引起的先天免疫反应的类型决定这一工作假设，该项目预计实现以下目标：

DESCRIPTION (provided by applicant): The immunopathogenesis associated with HIV-1 infection is characterized by several functional abnormalities of immune system cell populations and by a progressive decline in the numbers and functions of CD4+ T lymphocytes. In spite of many efforts, the mechanisms ultimately leading to the development of AIDS have not yet been fully elucidated. The general goal of this proposal is to characterize early HIV interactions as well as bystander effects of HIV-1 gene products on cell populations of the innate immunity system to the aim of defining novel mechanisms involved in viral persistence and immune system dysfunctions relevant to the comprehension of immunopathogenesis of AIDS. Based on the working hypothesis that the functional outcome of the immune response is likely to be determined by the type of innate immune response elicited, the project foresees the following objectives: i) Determine the effects of early HIV interaction with macrophages and DCs on the expression/activation of Toll-like receptors ii) Define the molecular signals triggered by early HIV/target cell interactions and their role in HIV mediated functional cell alterations iii) Characterize the immunomodulatory activities of HIV-1 Vpr accessory protein on effector cells linking innate and adaptive responses. It is expected that this research could provide the basis for a novel interpretation of important aspects of immunopathogenesis which may be critical to the ultimate development of effective prophylactic and therapeutic interventions.