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

S Kewenig, T Schneider, K Hohloch, K Lampe–Dreyer… - Gastroenterology, 1999 - Elsevier
S Kewenig, T Schneider, K Hohloch, K Lampe–Dreyer, R Ullrich, N Stolte, C Stahl–Hennig…
Gastroenterology, 1999Elsevier
Background & Aims: Human immunodeficiency virus (HIV) infection leads to severe
immunologic and functional disturbances in the intestinal tract in late stages of the disease.
Information on mucosal pathology directly after infection is limited. We characterized this
early phase in rhesus macaques infected with simian immunodeficiency virus (SIV).
Methods: Eight rhesus macaques were infected with SIV. Upper endoscopy was performed
at defined times before and after infection. Viral load, percentage of CD4+ T cells, villus …
Background & Aims
Human immunodeficiency virus (HIV) infection leads to severe immunologic and functional disturbances in the intestinal tract in late stages of the disease. Information on mucosal pathology directly after infection is limited. We characterized this early phase in rhesus macaques infected with simian immunodeficiency virus (SIV).
Methods
Eight rhesus macaques were infected with SIV. Upper endoscopy was performed at defined times before and after infection. Viral load, percentage of CD4+ T cells, villus height, crypt depth, and Ki-67–positive crypt cells were analyzed in duodenal biopsy specimens. Serum β-carotene and vitamin D levels were assessed.
Results
A rapid increase of duodenal SIV core protein (p27) concentration and an almost complete loss of intestinal CD4+ T cells was found within 2 weeks after infection. A decrease of villus height was observed, and the percentage of Ki-67–positive (proliferating) crypt cells increased. Serum concentrations of vitamin D decreased in 6 of 8 animals, and β-carotene concentrations decreased in 3 of 8 animals after infection.
Conclusions
Mucosal SIV replication and intestinal CD4+ T cell depletion are early events in SIV-infected rhesus macaques. The structural changes of the mucosa strongly support the concept of HIV/SIV–induced enteropathy. In contrast to late-stage human HIV infection, early small intestinal villous atrophy in SIV infection is associated with crypt hyperplasia. GASTROENTEROLOGY 1999;116:1115-1123
Elsevier