HIV MUCOSAL PATHOGENESIS IN PRIMARY INFECTION

原发感染中的 HIV 粘膜发病机制

• 批准号: 6650993
• 负责人: MICHAEL A POLES
• 金额: $ 12.61万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6650993
• 关键词: AIDS therapy; HIV infections; clinical research; flow cytometry; helper T lymphocyte; human subject; human therapy evaluation; intestinal mucosa; microorganism immunology; mucosal immunity; phenotype; polymerase chain reaction; virus genetics; virus load; virus receptors; virus replication

R. Poles' long-term career objective is to become a successful, independent investigator. As a independent investigator, his goal will be to produce funded, investigator-initiated, translational research of high scientific quality. His specific area of interest is the study of pathogenesis of human immunodeficiency virus (HIV) infection in the immune compartment of the gastrointestinal mucosa. This research will enable development of unique and superior methodology for surveillance of HIV patients prior to and during receipt of anti-retroviral agents as well as allowing for development of improved vaccination strategies. In order to achieve his goals, Dr. Poles has designed a three phase career development plan. The initial phase will consist of continuing didactic course work towards a doctoral degree from the Department of Microbiology and Immunology at UCLA. The second phase will be to initiate the research described below under the mentorship of Drs. Irvin Chen and John Walsh. The final phase will involve publication of the study findings and application for independent funding. The first aim of this study is to test the hypothesis that the gastrointestinal mucosa is a fundamental target for HIV in patients with primary infection by quantifying viral load in the tissue with PCR, and showing with flow cytometry and quantitative image analysis the effect of HIV infection on the CD4+ cells in the mucosa. The second aim will examine genotypic differences of virus derived from the blood and mucosa in untreated primary infection patients, and examining the phenotypic expression of these changes. Virus from the two compartments will be compared in terms of replication kinetics and co-receptor usage in co-culture assays. Through this series of experiments, Dr. Poles will attempt to determine the factors responsible for these evolutionary changes. The third aim will use the same techniques as the previous two aims, but specifically examine primary infection patients who have initiated treatment with highly potent antiviral therapy to examine its effects on these parameters.

R. Poles的长期职业目标是成为一名成功的独立调查员。作为一名独立研究者，他的目标是生产资助的，研究人员发起的高科学质量转化研究。他感兴趣的特定领域是研究胃肠道粘膜免疫区室中人类免疫缺陷病毒（HIV）感染的发病机理。这项研究将使在收到抗返回病毒药物之前和期间对HIV患者的监测进行独特和卓越的方法，并允许发展改善的疫苗接种策略。为了实现自己的目标，Poles博士设计了三个阶段的职业发展计划。初始阶段将包括持续的教学课程在UCLA微生物学和免疫学系的博士学位上工作。第二阶段是启动下面在DRS的指导下描述的研究。欧文·陈（Irvin Chen）和约翰·沃尔什（John Walsh）。最后阶段将涉及研究结果和独立资金的申请。这项研究的第一个目的是检验以下假设：胃肠道粘膜是原发性感染患者HIV的基本靶标，通过用PCR定量病毒载量，并通过流式细胞仪和定量图像分析显示HIV感染对Mucosa CD4+细胞的影响。第二个目的将检查未经治疗的原发性感染患者中血液和粘膜衍生的病毒的基因型差异，并检查这些变化的表型表达。在共培养测定中，将根据复制动力学和共受体使用来比较两个隔室的病毒。通过这一系列实验，Poles博士将尝试确定负责这些进化变化的因素。第三个目标将使用与前两个目的相同的技术，但专门检查了已经开始使用高度有效抗病毒药治疗治疗的原发性感染患者，以检查其对这些参数的影响。