Simian immunodeficiency virus infection of the gastrointestinal tract of 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 simian immunodeficiency virus (SIV) also exhibit diarrhea and weight loss; therefore, we investigated the use of this animal model to study HIV-associated intestinal abnormalities. A retrospective study of intestinal tissues from 15 SIV-infected macaques was performed to determine the cellular targets of the virus and examine the effect of SIV infection on jejunal mucosal morphology and function. Pathological and morphological changes included inflammatory infiltrates, villus blunting, and crypt hyperplasia. SIV-infected cells were detected by in situ hybridization in stomach, duodenum, jejunum, ileum, cecum, and colon. Using combined immunohistochemistry and in situ hybridization, the cellular targets were identified as T lymphocytes and macrophages. The jejunum of SIV-infected animals had depressed digestive enzyme activities and abnormal morphometry, suggestive of a maturational defect in proliferating epithelial cells. Our results suggest that SIV infection of mononuclear inflammatory cells in intestinal mucosa may alter development and function of absorptive epithelial cells and lead to jejunal dysfunction.
Department of Internal Medicine, University of California, Davis 95616.
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C
Heise
P
P
Vogel
C J
CJ
Miller
C H
CH
Halsted
S
S
Dandekar
D000818:Animals; D016516:CD4-CD8 Ratio; D004279:DNA, Viral / Q000235:genetics; D004195:Disease Models, Animal; D004848:Epithelium / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005767:Gastrointestinal Diseases / Q000382:microbiology / Q000473:pathology* / Q000503:physiopathology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D007583:Jejunum / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D008253:Macaca mulatta / Q000382:microbiology*; D008297:Male; D008871:Microvilli / Q000201:enzymology / Q000648:ultrastructure; D012189:Retrospective Studies; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000302:isolation & purification; D013393:Sucrase / Q000032:analysis; D013601:T-Lymphocytes / Q000473:pathology; D001616:beta-Galactosidase / Q000032:analysis
D004279:DNA, Viral; D001616:beta-Galactosidase; D013393:Sucrase