Arteriopathy in macaques infected with simian immunodeficiency virus

An arteriopathy characterized by intimal and medial thickening and fibrosis was seen in 19 of 85 rhesus monkeys infected with simian immunodeficiency virus (SIV), a lentivirus with morphologic, genetic, and biologic similarities to HIV-1 and HIV-2.

All cases of simian AIDS in rhesus monkeys at the New England Regional Primate Research Center, resulting from either experimental or naturally acquired SIV infection, were retrospectively examined for evidence of histopathologic changes to the vasculature. Of the 85 SIV-related deaths recorded in the pathology files to date, tissues from 19 animals were chosen for further study because of thickening, disruption, inflammation, or other abnormality to any layer of the vascular wall. The lesion was characterized by special stains, immunoperoxidase procedures, and ultrastructural examination.

Affected monkeys of both sexes varied in age from 4 months to 17 years at the time of inoculation and survived from 41 days to 4 years after infection. Pulmonary arteries were affected in all 19 animals, while vessels in other parenchymal organs were involved less frequently. In addition to sometimes marked intimal thickening with luminal occlusion, the internal elastic laminae were fragmented and interrupted. Seven of 19 animals had pulmonary thromboses with varying degrees of organization and recanalization. Immunohistochemical studies, special stains, and ultrastructural analyses revealed the thickened intimae to be composed predominantly of collagen, extracellular matrix, and smooth muscle cells. Ultrastructurally, endothelial cells from both early (no intimal thickening) and advanced lesions were plump, vacuolated, and often disorganized and detached from the subendothelial space. Increased numbers of macrophages (CD68+) were found in the adventitia and occasionally in the thickened intima and media. Rare, fully differentiated macrophages (CD68+, 25F9+) were demonstrated in lumina of affected vessels, some of which expressed p27 SIV gag protein. However, the lesion was not uniformly associated with localization of either viral protein or RNA at the site using immunohistochemistry or in situ hybridization, respectively. A similar arterial lesion has been described in children with AIDS.

The morphologic findings in macaques and their similarity to arteriosclerotic changes induced by experimental endothelial damage in other species collectively suggest that arteriopathy in AIDS may represent a manifestation secondary to primary endothelial injury.