MOLECULAR PATHOLOGY OF HIV/SIV ENTEROPATHY

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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.