SIMIAN IMMUNODEFICIENCY VIRUS-INFECTION OF THE GASTROINTESTINAL-TRACTOF RHESUS MACAQUES - FUNCTIONAL, PATHOLOGICAL, AND MORPHOLOGICAL-CHANGES

Gastrointestinal dysfunction and wasting are frequent complications of human immunodeficiency virus (HIV) infection. Nutrient malabsorption, decreased digestive enzymes and HIV transcripts have been documented in jejunal mucosa of HIV-infected patients; however, the pathogenesis of this enteropathy is not understood Rhesus macaques infected with si mian immunodeficiency virus (SIV) also exhibit diarrhea and weight los s; therefore, we investigated the use of this animal model to study HI V-associated intestinal abnormalities. A retrospective study of intest inal tissues from 15 SIV-infected macaques was performed to determine the cellular targets of the virus and examine the effect of SIV infect ion on jejunal mucosal morphology and function. Pathological and morph ological changes included inflammatory infiltrates, villus blunting, a nd crypt hyperplasia. SIV-infected cells were detected by in situ hybr idization in stomach, duodenum, jejunum, ileum, cecum, and colon. Usin g combined immunohistochemistry and in situ hybridization, the cellula r targets were identified as T lymphocytes and macrophages. The jejunu m of SIV-infected animals bad depressed digestive enzyme activities an d abnormal morphometry, suggestive of a maturational defect in prolife rating epithelial cells. Our results suggest that SIV infection of mon onuclear inflammatory cells in intestinal mucosa may after development and function of absorptive epithelial cells and lead to jejunal dysfu nction.