SIV INFECTION MODEL OF HIV INFECTION/DISEASE HIV ENTEROPATHY, GALT RESTORATION

HIV 感染/疾病的 SIV 感染模型 HIV 肠病、GALT 恢复

• 批准号: 8172480
• 负责人: Francois J Villinger
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 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/8172480
• 关键词: Agonist; Animals; Architecture; Bacterial Translocation; Biological Markers; Blood; Cells; Chronic; Clinical; Computer Retrieval of Information on Scientific Projects Database; Disease; Funding; Gastrointestinal tract structure; Grant; HIV; HIV Enteropathy; HIV Infections; Immune response; Infection; Infiltration; Inflammation; Inflammatory; Institution; Intestines; Lead; Lentivirus Infections; Lymphoid Tissue; Macaca mulatta; Maintenance; Malabsorption Syndromes; Modeling; Monitor; Non-Rodent Model; Oral Administration; Patients; Permeability; Plasma; Research; Research Personnel; Resources; SIV; Source; Tissues; United States National Institutes of Health; Villus; Viral Load result; Viremia; gastrointestinal; immune activation; microbial; reconstitution; repaired; research study; restoration

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. HIV and SIV replication has been highlighted to predominantly occur in the GI tract contributing to most of the viremia detected in blood. As a consequence of such localized active infection, HIV infected patients experiment malabsorption early on as well as signs of GI inflammation leading to increased GI permeability and even bacterial translocation. FXR agonists have been shown to favorably impact maintenance of intestinal mucosal barrier integrity, inflammatory cell infiltration and villus architecture in rodent models of non-HIV enteropathy. Our initial hypothesis suggests that the treatment of an SIV-infected animal with an FXR agonist will aid in the restoration and repair of the gut tissue and subsequently lead to a decrease in microbial translocation and associated effects. As an extension of this hypothesis, we propose to explore a treatment with an FXR agonist on the course of SIV infection. We hypothesize that the chronic treatment with an FXR agonist will benefit the gut tissue in chronic SIV infection leading to improvement in markers of enteropathy, decreased evidence of microbial translocation, decreased systemic immune activation and/or increased reconstitution of gastrointestinal associated lymphoid tissue. For this pilot proposal, a set of 5 rhesus macaque chronically infected with SIV are being treated daily with the FXR agonist via oral administration. Plasma biomarkers, viral loads and immune responses are being monitored as well as the GI permeability and tissue architecture, to document the potential clinical benefit of such therapy in chronic lentivirus 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。 HIV和SIV复制已被突出显示，主要发生在胃肠道中，导致大多数在血液中检测到的病毒血症。由于这种局部活性感染，HIV感染的患者早期实验吸收不良以及胃肠道炎症的迹象，导致胃肠道渗透性增加甚至细菌易位。 FXR激动剂已显示出对非HIV肠病啮齿动物模型中肠粘膜屏障完整性，炎症细胞浸润和绒毛结构的维持。 我们的最初假设表明，用FXR激动剂对SIV感染的动物的处理将有助于恢复和修复肠道组织，并随后导致微生物易位和相关作用减少。作为该假设的扩展，我们建议在SIV感染过程中探索与FXR激动剂的治疗方法。 我们假设使用FXR激动剂的慢性治疗将使慢性SIV感染中的肠道组织有益，从而改善肠病标志，降低微生物易位的证据，降低全身免疫激活和/或增加胃肠道相关淋巴组织的结构。对于此试点提案，每天通过口服给予FXR激动剂治疗一组5个恒河猕猴长期感染了SIV。血浆生物标志物，病毒载荷和免疫反应以及GI渗透性和组织结构正在监测，以记录这种治疗在慢性慢病毒感染中的潜在临床益处。