Crosstalk Among Oral & Gastrointestinal Soluble Innate Factors, HIV, & Microbes

描述（由申请人提供）：本提案提交给NIDCR PAR-05-031，“与艾滋病毒/艾滋病相关的口腔表现的多学科研究”。我们的提案，“口腔和胃肠道可溶性先天因素，艾滋病毒和微生物之间的串扰”正在提交纽约大学牙科学院（NYUCD），与丹尼尔马拉默德博士作为首席研究员。马拉默德博士为纽约大学艾滋病研究所、纽约大学医学院和亚伦·戴蒙德艾滋病研究中心召集了一批才华横溢的研究人员，这些研究中心都位于纽约市第一大道上，相距仅几个街区。该提案包括4个相互关联的研究项目，一个行政/生物统计核心和一个临床核心。整个方案使用相同的病例对照研究人群，包括85例HIV+、HAART初治受试者，随后将开始抗逆转录病毒治疗。还将有一个类似的HIV受试者队列。临床中心将获得口腔和GI样本，监测患者进展，进行完整的口腔健康检查，并保存所有受试者记录。项目1（Linqi Zhang博士，ADARC）将确定全唾液蛋白质组，比较HIV-、HIV+/HAART初治和HIV+ HAART后样本。研究将集中在可溶性分子，是宿主先天防御系统的一部分。项目2（Yihong Li博士，NYUCD）将定义HAART前后HIV与HIV+唾液样本和HIV+的口腔微生物群。研究将集中在整体微生物多样性，以及艾滋病毒感染后改变的细菌的定量，和/或与龋齿和牙周病有关的细菌。项目3（Michael Poles博士，NYUSoM）将使用内窥镜检查研究胃肠道的其余部分，以获得液体和活检样本。他的研究将集中在先天免疫介质和GI微生物，并将他的数据与项目1和2进行比较。项目4（丹尼尔马拉默德博士，纽约大学）将研究唾液中的抗菌和抗病毒活性，重点是先天宿主防御系统。此外，他将确定在体外感染口腔与直肠组织的能力，并比较从口腔、GI和血液中获得的HIV-1变体。行政/生物统计核心（Malamud博士和Norman博士）将通过执行委员会和外部咨询委员会监督整个研究。所有数据和统计分析将由该核心处理。总体目标是确定宿主防御分子和细菌在HIV感染和随后的抗逆转录病毒治疗中的相互作用。

DESCRIPTION (provided by applicant): This proposal is being submitted to the NIDCR PAR-05-031, "Multidisciplinary Research on Oral Manifestations Associated with HIV/AIDS". Our proposal, "Crosstalk among oral and gastrointestinal soluble innate factors, HIV and microbes" is being submitted by NYU College of Dentistry (NYUCD), with Dr. Daniel Malamud as principal investigator. Dr. Malamud has assembled a talented group of investigators for NYUCD, NYU School of Medicine (NYUSoM) and the Aaron Diamond AIDS Research Center (ADARC), all located within a few blocks of each other on First Avenue in New York City. The proposal consists of 4 interrelated research projects, an Administrative/Biostatistical Core and a Clinical Core. The entire proposal utilizes the same case controlled study population consisting of 85 HIV+, HAART naive subjects who will subsequently begin antiretroviral therapy. There will also be a similar cohort of HIV- subjects. The clinical core will obtain oral and Gl samples, monitor patient progress, carry out complete oral health examinations, and maintain all subject records. Project 1 (Dr. Linqi Zhang, ADARC) will determine the whole saliva proteome comparing HIV-, HIV+/HAART naive, and HIV+ post-HAART samples. Studies will focus on soluble molecules that are part of the host innate defense system. Project 2 (Dr Yihong Li, NYUCD) will define the oral microbiota in HIV vs. HIV+ saliva samples and HIV+ before and after HAART. Studies will focus on overall microbial diversity, and quantitation of bacteria that are altered after HIV infection, and/or related to caries and periodontal disease. Project 3 (Dr. Michael Poles, NYUSoM) will study the remainder of the Gl track using endoscopy to obtain fluid and biopsy samples. His study will focus in innate immune mediators and Gl microbes, and his data compared to Projects 1 and 2. Project 4 (Dr. Daniel Malamud, NYUCD) will study antibacterial and antiviral activities in saliva, focusing on the innate host defense system. In addition he will determine the ability to infect buccal vs. rectal tissue in vitro, and compare the HIV-1 variants obtained from oral, Gl and blood. The Administrative/Biostatistical Core (Drs. Malamud and Norman) will oversee the entire study via an Executive Committee and an External Advisory Committee. All data and statistical analyses will be handled by this core. The overall goal is to define the interactions between host defense molecules and bacteria in HIV infection and subsequent antiretroviral therapy.