HIV MUCOSAL PATHOGENESIS IN PRIMARY INFECTION

R.Poles的长期职业目标是成为一名成功的、独立的调查员。作为一名独立的研究人员，他的目标将是产生受资助的、由研究人员发起的、高科学质量的转化性研究。他感兴趣的具体领域是研究人类免疫缺陷病毒(HIV)感染在胃肠道粘膜免疫隔间的发病机制。这项研究将有助于制定独特和优越的方法，在接受抗逆转录病毒药物治疗之前和期间对艾滋病毒患者进行监测，并允许制定改进的疫苗接种战略。为了实现自己的目标，波尔斯博士设计了一个分三个阶段的职业发展计划。最初阶段将包括加州大学洛杉矶分校微生物学和免疫学系继续讲授课程，以获得博士学位。第二阶段将在欧文·陈博士和约翰·沃尔什博士的指导下启动下文所述的研究。最后阶段将包括发表研究结果和申请独立资助。这项研究的第一个目的是通过用聚合酶链式反应定量组织中的病毒载量，并用流式细胞仪和定量图像分析显示HIV感染对粘膜中CD4细胞的影响，来检验胃肠道粘膜是HIV感染患者的基本靶点的假设。第二个目标是检查未经治疗的原发感染患者血液和粘膜中病毒的基因类型差异，并检查这些变化的表型表达。来自两个隔室的病毒将在复制动力学和共培养试验中的共受体使用方面进行比较。通过这一系列实验，波尔斯博士将试图确定导致这些进化变化的因素。第三个目标将使用与前两个目标相同的技术，但具体检查已开始使用高效抗病毒治疗的初发感染患者，以检查其对这些参数的影响。

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.