CHARACTERIZATION OF THE CUTANEOUS EXANTHEM IN MACAQUES INFECTED WITH A NEF GENE VARIANT OF SIVMAC239

The molecularly cloned viruses known as SIVmac239/ R17Y and SIVmac239/ YEnef cause extensive lymphocyte activation and induce an acute diseas e syndrome in macaque monkeys. One manifestation of this syndrome is a severe diffuse cutaneous maculopapular exanthem that is similar to th e exanthem associated with HIV-1 infection. To examine the pathogenesi s of this exanthem biopsies obtained throughout the course of clinical ly evident rash were examined for the presence of virus by in situ hyb ridization and immunohistochemistry, and the cellular infiltrate was c haracterized with respect to cellular immunophenotype and chemokine re ceptor expression. The onset of rash was associated with abundant simi an immunodeficiency virus nucleic acid and protein within perivascular dermal infiltrates and occasionally within intraepithelial cells. Ana lysis of cellular infiltrates showed that biopsies, obtained on the da y of rash onset, were composed of equal numbers of CD4+ and CD8+ lymph ocytes and abundant alpha E beta 7 positive cells surrounding vessels with upregulated endothelial E-selectin. Moreover, by examining virus expression in sequential skin biopsies from the same animal, the clear ance of virus and the resolution of rash were associated with an incre ase in the percentage of cells expressing CD8, the chemokine receptor CXCR3, and GMP-17, a marker of cytotoxic granules. These results sugge st that activated cytotoxic T cells are trafficking to sites of inflam mation in the skin and directly or indirectly affect levels of viral r eplication at these sites.