Rapid mucosal CD4(+) T-cell depletion and enteropathy in simian immunodeficiency virus-infected rhesus macaques

Background & Aims: Human immunodeficiency virus (HIV) infection leads to se vere immunologic and functional disturbances in the intestinal tract in lat e stages of the disease. Information on mucosal pathology directly after in fection is limited. We characterized this early phase in rhesus macaques in fected with simian immunodeficiency virus (SIV). Methods: Eight rhesus maca ques were infected with SIV. Upper endoscopy was performed at defined times before and after infection. Viral load, percentage of CD4(+) T cells, vill us height, crypt depth, and Ki-67-positive crypt cells were analyzed in duo denal biopsy specimens. Serum beta-carotene and vitamin D levels were asses sed. Results: A rapid increase of duodenal SIV core protein (p27) concentra tion and an almost complete loss of intestinal CD4(+) T cells was found wit hin 2 weeks after infection. A decrease of villus height was observed, and the percentage of Ki-67-positive (proliferating) crypt cells increased. Ser um concentrations of vitamin D decreased in 6 of 8 animals, and beta-carote ne concentrations decreased in 3 of 8 animals after infection. Conclusions: Mucosal SIV replication and intestinal CD4(+) T cell depletion are early e vents in SIV-infected rhesus macaques. The structural changes of the mucosa strongly support the concept of HIV/SIV-induced enteropathy. In contrast t o late-stage human HIV infection, early small intestinal villous atrophy in SIV infection is associated with crypt hyperplasia.