EARLY MECHANISMS OF HIV TRANSMISSION USING THE SIV/MACAQUE MODEL FOR AIDS

使用艾滋病病毒/猕猴模型研究艾滋病毒传播的早期机制

• 批准号: 8172686
• 负责人: Marie-Claire Elisabeth Gauduin
• 金额: $ 1.92万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172686
• 关键词: AIDS Vaccines; Accounting; Acquired Immunodeficiency Syndrome; CD4 Positive T Lymphocytes; Cells; Computer Retrieval of Information on Scientific Projects Database; Dendritic Cells; Development; Dissection; Epidemic; Funding; Generations; Genital system; Grant; HIV; Human; Immune response; Immunization; In Situ; Infection; Institution; Knowledge; Lymphocyte; Macaca; Macaca fascicularis; Methods; Modeling; Pathway interactions; Phenotype; Research; Research Personnel; Resources; SIV; Sexual Transmission; Site; Source; Sterility; Surface; Time; United States National Institutes of Health; Vaccines; Vagina; Viral; Virus Diseases; cell type; intraepithelial; macrophage; mucosal site; novel vaccines; prevent; rectal; success; transmission process; vaginal transmission

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sexual transmission of human immunodeficiency virus (HIV) accounts for the majority of new infections worldwide. A vaccine capable of preventing sexual transmission across genital or rectal mucosal surfaces could provide a method for stopping the AIDS epidemic. The ultimate success of strategies to prevent sexual transmission of HIV depends, in part, on a better understanding of the virological and immunological mechanisms that underlie sexual transmission. Numerous studies have demonstrated the difficulty to achieve sterile protection from vaginally or rectally acquired HIV/SIV using parenteral immunization. Mucosal immunization is seen as the best approach to achieve sustainable immune responses at mucosal sites of viral entry. Defining the mechanisms of vaginal HIV transmission, in particular the initial immune response is central to the development of effective strategies to develop a successful mucosal AIDS vaccine. Our knowledge of the initial target cells involved in mucosal transmission is still evolving. Increasing evidence suggests that the initial site of productive infection occurs in situ at the mucosal surface. Studies of vaginal transmission suggest that the potential initial target cell may be either activated CD4+ T cells or intraepithelial dendritic cells. Precise dissection of viral targets and pathways involved in sexual HIV transmission will prove essential to the global effort to develop a protective vaccine. The identification of initial target cells and the ability to elicit and to enhance cellular or humoral immune responses at mucosal sites is likely to be a crucial step in the development of novel vaccines. These questions are extremely difficult to pursue experimentally in humans. In this study we propose to examine in situ viral infection at mucosal portal of entry in the SIV/cynomolgus (Macaca fascicularis) macaque model using SIV tagged with GFP. Specific aims will include: 1) To identify the types of cells initially infected (i.e., lymphocytes, macrophages, and dendritic cells), their phenotype and function; 2) To investigate the mechanisms, time course, and pathways of viral spread from site of initial infection; and, 3) To explore generation of early mucosal cellular immune response at vaginal site of SIV infection.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 人类免疫缺陷病毒（HIV）的性传播占全球大部分新感染。能够防止跨生殖器或直肠粘膜表面性传播的疫苗可以提供阻止艾滋病流行病的方法。防止艾滋病毒性传播的策略的最终成功取决于对性传播基础的病毒学和免疫学机制的更好理解。大量研究表明，使用肠胃外免疫获得无菌保护免受阴道或直肠获得的HIV/SIV的困难。粘膜免疫被视为在病毒进入的粘膜部位实现可持续免疫反应的最佳方法。定义阴道HIV传播的机制，特别是最初的免疫反应对于开发成功的粘膜艾滋病疫苗的有效策略的发展至关重要。我们对粘膜传播涉及的最初靶细胞的了解仍在发展。越来越多的证据表明，生产感染的初始部位发生在粘膜表面的原位。阴道传播的研究表明，潜在的初始靶细胞可以被激活的CD4+ T细胞或上皮内树突状细胞。对性HIV传播涉及的病毒靶标和途径的精确解剖将被证明是全球开发保护性疫苗的努力至关重要的。初始靶细胞的鉴定以及在粘膜部位引起和增强细胞或体液免疫反应的能力可能是新型疫苗开发的关键步骤。这些问题在人类中很难实验。在这项研究中，我们建议使用用GFP标记的SIV检查SIV/Cynomolgus（Macaca fascicularis）猕猴模型的粘膜入口处的原位病毒感染。 具体目的包括：1）确定最初感染的细胞类型（即淋巴细胞，巨噬细胞和树突状细胞），其表型和功能； 2）研究从初始感染部位的病毒传播的机制，时间过程和途径； 3）探索SIV感染阴道部位的早期粘膜细胞免疫反应的产生。