Simian immunodeficiency virus infection of macaques: end-stage disease is characterized by widespread distribution of proviral DNA in tissues.

Four simian immunodeficiency virus (SIV)-infected macaques in the terminal stages of AIDS were studied. Easily detectable unintegrated proviral DNA was present in nearly every tissue (lymphoid and nonlymphoid) examined. SIV-specific immunohistochemistry revealed that macrophages or macrophage-like cells were the predominant reservoirs for SIV. High burdens of infectious SIV were also characteristic of end-stage disease. At the molecular level, sequence analyses of molecular clones derived directly from tissue demonstrated that SIV, like other RNA viruses, exists as a mixture of closely related genomes. Viruses derived by cocultivation seemed to be selected for their ability to grow in tissue culture and did not represent the wide spectrum of genotypes in tissues. These data indicate that SIV-induced immunodeficiency is a complex, multisystem disease and that SIV replication, in addition to impairing the immune system, may have direct deleterious effects on multiple organ systems.