MOLECULAR PATHOLOGY OF HIV/SIV ENTEROPATHY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 胃肠道是HIV/SIV感染和CD 4 + T细胞耗竭的主要靶点。对粘膜免疫系统的损害与统称为AIDS肠病的各种GI表现有关;通常以慢性腹泻和消瘦为特征。虽然我们对HIV/SIV肠病的理解最近有了很大的提高，但最近发现的microRNAs（miRNAs）又增加了另一种新的复杂的基因表达调控因子，在这种疾病的分子发病机制中具有潜在的作用。miRNA是约21-23个核苷酸的非编码RNA，高度保守，通过靶向mRNA进行翻译抑制或降解来抑制基因表达。虽然miRNA研究在各种类型的癌症中被广泛报道，并且在心脏病、神经病、代谢病和皮肤病中的发病率越来越高，但它们在特发性胃肠道疾病如HIV/SIV肠病中的作用尚不清楚，有待解决。为了更好地理解胃肠道疾病的分子机制，我们将在SIV感染（PI）之前和之后21天、3个月、6个月和尸检时连续分析相同动物肠道中的总体miRNA表达谱。更重要的是，我们将分别研究不同粘膜成分（上皮内淋巴细胞，固有层淋巴细胞，上皮和纤维血管基质）中的miRNA表达谱，以更好地了解HIV/SIV诱导的GI疾病/功能障碍的发病机制。该项目已分配了4只动物，研究目前正在进行中。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The gastrointestinal (GI) tract is a major target of HIV/SIV infection and CD4+ T cell depletion. The damage to the mucosal immune system is associated with a variety of GI manifestations collectively called AIDS enteropathy; generally characterized by chronic diarrhea, and wasting. Although our understanding of HIV/SIV enteropathy has greatly improved lately, the recent discovery of microRNAs (miRNAs) has added yet another novel and complex regulator of gene expression with potential roles in the molecular pathogenesis of this disorder. miRNAs are ~21-23 nucleotide noncoding RNAs, highly conserved and suppress gene expression by targeting mRNAs for translational repression or degradation. While miRNA studies are being reported extensively in various types of cancer, and at increasing rates in cardiac, neurological, metabolic and skin diseases, their role in idiopathic GI disorders such as HIV/SIV enteropathy is unknown and yet to be addressed. To better understand the molecular mechanisms underlying GI disease we will analyze global miRNA expression profiles sequentially in the intestine of the same animals prior to and at 21 days, 3, 6 months and necropsy following SIV infection (PI). More importantly we will examine miRNA expression profiles in distinct mucosal components (intraepithelial lymphocytes, lamina propria lymphocytes, epithelium and fibrovascular stroma) separately to better understand the pathogenesis of HIV/SIV induced GI disease/dysfunction. Four animals have been assigned to the project and study is currently in progress.