Systemic and intestinal immune responses to HIV-2(287) infection in Macacanemestrina

Nonhuman primate models of human AIDS have been used successfully to evalua te candidate vaccines and infection intervention therapies. Successes of pa thogenicity studies in primate models have been limited because of the vari ed infection outcomes and characteristic low number of study animals. The a cutely pathogenic HIV-2(287)-Macaca nemstrina model has shown promise both in antiviral drug evaluation and in pathogenicity studies. Here we describe virus replication, spread, and host responses during the first 28 days of HIV-2(287) infection. Focusing on 18 macaques from a larger 27-macaque stud y, we report changing virus loads, CD4(+) cell depletions, and antibody res ponses both systemically and in the mucosa of the small intestine. After in travenous inoculation, blood and intestinal tissue were collected from pair s of macaques at 12 hr and 1, 2, 4, 6, 10, 14, 21, and 28 days postinfectio n. Specimens were examined for evidence of infection by quantitative cultur es, in situ hybridization, lymphocyte subset monitoring, and antibody produ ction. The data were presented serially as though all samples were collecte d from a single macaque. The highest blood virus loads were detected betwee n days 10 and 14 and subsequently decreased through day 28. This coincided with a significant increase in ileum mucosa virus loads on day 10, which be came undetectable by day 28. The lowest levels of CD4(+) cells were observe d on days 21 and 28 in blood and ileum mucosa. CD4(+):CD8(+) cell ratios in blood and ileum dropped dramatically after day 10 to lowest levels by day 28. Intestinal virus loads were inversely correlated with CD4(+) cell and v irus-specific antibody levels in the ileum after day 6. These results under score the suitability of this model for pathogenicity studies as well as th e importance of the intestinal lymphoid tissues as an initial site of virus replication and cell destruction during the acute, asymptomatic stage of A IDS development.