Study objectives prospectively assessed association between SIV infection, histopathologic changes, jejunal bacterial flora, clinical malabsorption and nutritional status. We prospectively studied 12 juvenile rhesus macaques (nine SIV-infected, three uninfected controls). Samples were taken preinoculation 1, 2, 4, 8, 12, 24, 40 and 52 weeks postinoculation (pi). Necropsy tissue from three asymmptomatic animals killed at one, two, and four weeks pi, and four that died of AIDS at weeks 12, 36, 48 and 55, were evaluated. Serial jejunal biopsies were obtained for SIV localization, histopathology and digestive enzyme activities. Cellular targets of SIV were determined by combined in situ hybridization and immunohistochemistry using antibodies for T cells and macrophages. Clinical malabsorption was determined by sucrose or D-xylose administration. SIV-infected T cells and macrophages were detected throughout the gastrointestinal tracts in all animals. Animals that died of AIDS had diarrhea, wasting, D-xylose malabsorption, and significantly reduced levels of folate, vitamin A and zinc. All but one SIV-infected monkey, exhibited malabsorption by increased breath hydrogen following sucrose and/or decreased blood D-xylose. 5/9 Animals malabsorbed between weeks 1-4 pi. At all timepoints, jejunal aspirates contained normal bacterial flora and no evidence of upper gastrointestinal bacterial overgrowth. Giardia or cryptosporidia were not detected in any samples. Common histopathological findings of intestinal biopsies included excessive cellular debris in the lamina propria and epithelium, lymphoplasmacytic infiltrates and cytoplasmic vacuoles in crypt epithelial cells. These results demonstrate that SIV-associated enteropathy and malabsorption can occur prior to advanced clinical complication of disease and that severe intestinal complications are associated with malabsorption and malnutrition in the terminal stages of AIDS. Expression of cell adhesion molecules and cytokines in intestinal mucosa was examined following siv infection. An upregulation of these epigenetic factors was observed correlating with viral load and clinical disease.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
2P51RR000169-34
Application #
3742076
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
34
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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