FACTORS INFLUENCING ORAL TRANSMISSION OF SIV

影响 SIV 口腔传播的因素

• 批准号: 8172677
• 负责人: Donald L Sodora
• 金额: $ 9.91万
• 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/8172677
• 关键词: Acquired Immunodeficiency Syndrome; African; Animal Model; Biological Models; Blood; Breast Feeding; Cells; Cellular Tropism; Child; Chronic Disease; Computer Retrieval of Information on Scientific Projects Database; Disease Progression; Dose; Event; Funding; Gingivitis; Goals; Grant; HIV; HIV Infections; HIV-1; Human; Human Milk; Immune; Immune response; Immunity; Infection; Infection prevention; Inflammation; Institution; Knowledge; Laboratories; Macaca; Macaca mulatta; Membrane; Modeling; Mothers; Mucous Membrane; Nature; Oral; Oral Sex; Oral cavity; Oral mucous membrane structure; Pathogenesis; Pattern; Primates; Probability; Proteins; Regimen; Research; Research Personnel; Resources; Route; SIV; Sampling; Seminal fluid; Source; Surface; Time; Tissues; United States National Institutes of Health; Vaccines; Vertical Disease Transmission; Viral; Virus; Work; design; experience; immune activation; lymph nodes; mucosal site; success; transmission process

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. Currently, more than 40 million people worldwide are persistently infected with HIV-1. Similar to HIV infection in humans, SIV infection in non-African primate species results in chronic disease that culminates in AIDS. The well-defined SlV infection of rhesus macaques is an excellent animal model system to assess HIV transmission and pathogenesis for several reasons. SIV infection In macaques closely resembles many aspects of HIV infection in humans including events associated with transmission, cellular tropism of the virus, viral replication patterns. disease progression, and the nature of the host immune response. Furthermore, the SIV/macaque model is important because knowledge of the time, route, and number of viral exposures Is known, the viral stock used to infect the macaques is well-characterized, and there is the ability to frequently sample important tissues (blood, lymph nodes, mucosal sites, etc) throughout infection. For HIV and SIV, the major mode of transmission for new infections is mucosal transmission, i.e. the virus has to pass through a mucosal membrane to infect the new host However, the probability to become infected from a mucosa] encounter is actually quite low. A variety of factors contribute to this low probability, including inhibitory proteins at mucosal surfaces, the difficulty to pass an intact mucosal membrane and the probability for the virus to find a suitable target cell to Infect Initially as soon as it passes the membrane. Using the macaque model, our laboratory has focused its work on oral transmission of HlV/SIV, a route that is important for mother-to-child (vertical) transmission through breast feeding and for transmission during oral sex when virus is present in semen. However, it still remains unclear what the most important events are which permit the actual transmission itself. Here we expand upon our previous findings by assessing the impact of immune activation on the transmission of SIV administered into the oral cavity of macaques. We hypothesize that higher levels of immune activation will increase the potential for SIV to elicit a productive infection. These studies will utilize a low dose regimen of viral Inoculations to mimic the viral levels that are present in breast milk and semen. We will assess transmission of SIV while the mucosa is experiencing a state of immune activation, gingivitis. Gingivitis is a common inflammation of the oral mucosa in humans and therefore may be impacting oral transmission in humans exposed to HIV containing semen (through receptive oral intercourse). These studies assessing the impact of the immune response on oral transmission are likely be applicable to other sites of mucosal transmission, and will be important for determining the immune mechanisms that impact the success of SIV/HIV mucosal transmission. Our long term goal is to utilize these findings to aid in the design of SIV/HlV vaccines that are able to elicit sterilizing immunity by preventing the infection of the first target cell when mucosal sites are exposed to HIV/SIV.

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。 目前，全世界有超过4000万人持续感染HIV-1。与人类的艾滋病毒感染相似，非非洲灵长类动物的SIV感染导致慢性疾病达到艾滋病。定义明确的SLV感染猕猴是出色的动物模型系统，可用于评估HIV传播和发病机理，原因有几个原因。猕猴中的SIV感染与人类中HIV感染的许多方面相似，包括与传播相关的事件，病毒的细胞向性，病毒复制模式。疾病进展和宿主免疫反应的性质。此外，SIV/猕猴模型很重要，因为知道了时间，路线和病毒暴露的知识，用于感染猕猴的病毒储备是充分表现的，并且在整个感染过程中都有经常采样重要的组织（血液，淋巴结，粘膜等）。对于艾滋病毒和SIV，新感染的主要传播方式是粘膜传播，即病毒必须通过粘膜膜以感染新宿主，但是，从粘膜中感染的可能性实际上很低。多种因素导致了这种低概率，包括粘膜表面处的抑制性蛋白质，通过完整的粘膜膜的困难以及病毒找到合适的靶细胞最初感染一旦通过膜就感染的概率。使用猕猴模型，我们的实验室将其工作重点放在HLV/SIV的口服传播上，这对于通过母乳喂养的母亲到子女（垂直）传播很重要的途径，在精液中存在病毒时在口交期间传播。但是，仍然不清楚最重要的事件是什么允许实际传输本身。在这里，我们通过评估免疫激活对猕猴口腔中的SIV传播的影响来扩展我们以前的发现。我们假设较高水平的免疫激活将增加SIV引起生产性感染的潜力。这些研究将利用病毒接种的低剂量方案来模仿母乳和精液中存在的病毒水平。我们将评估SIV的传播，而粘膜正在经历免疫激活状态，即牙龈炎。牙龈炎是人类口腔粘膜的常见炎症，因此可能会影响暴露于含有精液的HIV的人的口腔传播（通过接受性口服性交）。这些评估免疫反应对口腔传播影响的研究可能适用于其他粘膜传播部位，对于确定影响SIV/HIV粘膜传播成功的免疫机制非常重要。我们的长期目标是利用这些发现来帮助设计SIV/HLV疫苗的设计，这些疫苗能够通过防止粘膜位点暴露于HIV/SIV时防止第一个靶细胞的感染来引起免疫免疫。