Factors/HIV-1 Nef's Ability to Direct Immune Evasion

因素/HIV-1 Nef 引导免疫逃避的能力

• 批准号: 7384404
• 负责人: MARTHA J LEWIS
• 金额: $ 6.35万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2010-02-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7384404
• 关键词: Acquired Immunodeficiency Syndrome; Acute; Address; Affect; Animal Model; Antigen Presentation; Antiviral Agents; Area; CD8-Positive T-Lymphocytes; Cells; Class; Communicable Diseases; Communities; Containment; Cytotoxic T-Lymphocytes; Data; Development Plans; Down-Regulation; Environment; Epitopes; Equilibrium; Evolution; Generations; Goals; HIV; HIV Infections; HIV vaccine; HIV-1; Immune; Immune response; Immune system; Immunization; Immunology; In Vitro; Infection; Internal Medicine; Knowledge; Life Cycle Stages; MHC Class I Genes; Mediating; Medical; Medical Genetics; Mentorship; Methods; Microbiology; Mutation; Pathogenesis; Pharmaceutical Preparations; Play; Postdoctoral Fellow; Principal Investigator; Proteins; Relative (related person); Research; Research Personnel; Research Proposals; Resistance; Resources; Role; Science; Secondary to; Students; Surface; Therapeutic; Training; Vaccines; Viral; Viral Antigens; Viral Physiology; Viral Proteins; Viremia; Virus; Work; Yang; career; fitness; in vivo; killings; medical schools; member; nef Protein; pressure; programs; response; skills; therapeutic vaccine; virology

This application outlines a 4 year plan for the development of a career in medical science within the Division of Infectious Disease at the UCLA School of Medicine. Its Principal Investigator has completed training in Internal Medicine and graduate work in the field of medical virology. As a fellow in the Division of Infectious Diseases and member of the UCLA Subspecialty Training and Advanced Research (STAR) program she now details a plan to expand her knowledge and skills in the area of medical virology and immunology in order to become an independent investigator. The proposed program will be carried out under the mentorship of Dr. Otto Yang, a very well-respected, successful member of both the Division of Infectious Diseases and Microbiology, Immunology, and Medical Genetics. Dr. Yang has successfully supervised post-doctoral fellows and graduate students and is an expert in the field of HIV immunology. In particular his research group is a leader in the study of cytotoxic T lymphocyte (CTL) responses to HIV-1 infection. The UCLA research community with its numerous resources and opportunites will provide an excellent environment for the completion of the proposed research plan. The plan focuses on investigating factors influencing the HIV-1 accessory protein Nefs ability to mediate evasion of CTL immune responses. Previous studies by Dr. Yang and others showed that Nef down-regulates MHC Class I on infected cells making them less sensitive to killing by CTLs. The specific aims to be addressed include the following: 1. What factors affect the influence of Nef-mediated MHC-I downregulation on HIV-1 resistance to CTL? 2. What are the impacts of Nef-specific and non-Nef-specific CTLs on Nefs MHC down-regulatory function? 3. What are the relative selective pressures exerted by Nef-specific and non-Nef-specific CTLs on Nef sequence evolution? A combination of in vitro and in vivo methods will be utilized in order to explore the balance between host immune forces which favor the loss of Nefs function and viral forces which favor the retention of Nefs ability to down-regulate MHC I and thus evade CTL killing. The results of these studies are anticipated to further our knowledge of how the immune system works to control HIV-1 infection. This knowledge will help in the ongoing quest for an effective vaccine against HIV.

该应用程序概述了四年计划，以发展医学职业 加州大学洛杉矶分校医学院的传染病科。它的主要调查员已经完成 内科培训医学病毒学领域。作为分区的家伙 传染病和UCLA亚专业培训和高级研究（Star）的成员 她现在详细介绍了一项计划，以扩大医学病毒学领域的知识和技能和技能 免疫学成为一名独立研究者。 拟议的计划将在Otto Yang博士的指导下进行，这是一个非常受人尊敬的， 成功的成员是传染病和微生物学，免疫学和医学的成员 遗传学。杨博士成功监督了博士后研究员和研究生，是 HIV免疫学领域的专家。特别是他的研究小组是细胞毒性研究的领导者 淋巴细胞（CTL）对HIV-1感染的反应。 加州大学洛杉矶分校的研究社区拥有众多的资源和机会，将提供出色的 完成拟议的研究计划的环境。该计划重点是调查因素 影响HIV-1辅助蛋白NEFS介导CTL免疫反应逃避的能力。以前的 Yang博士和其他人的研究表明，NEF在受感染细胞上的MHC I类下调 对被CTL杀死的敏感不太敏感。要解决的具体目的包括以下内容：1。什么因素 影响NEF介导的MHC-1下调对HIV-1对CTL的抗性的影响？ 2。什么是 NEF特异性和非NEF特异性CTL对NEFS MHC下调函数的影响？ 3。什么是 NEF序列演变上由NEF特异性和非NEF特异性CTL施加的相对选择性压力？ 将利用体外和体内方法的组合来探索宿主之间的平衡 有利于NEFS功能和病毒力的损失的免疫力，有利于NEFS能力的保留 下调MHC I，从而逃避CTL杀戮。 预计这些研究的结果将进一步了解免疫系统如何起作用 控制HIV-1感染。这些知识将有助于持续寻求针对艾滋病毒的有效疫苗。