Eradication of human immunodeficiency virus 1 (HIV-1) from an infected individual cannot be achieved using current antiretroviral
therapy (ART) regimens. Viral reservoirs established in early
infection remain unaffected by ART and are able to replenish systemic
infection upon treatment interruption. Simian immunodeficiency virus (SIV) infected macaque models are useful for studying HIV pathogenesis, treatments, and persistent viral reservoirs. Here, we used the SIV macaque model to examine and quantify
RNA and
DNA positive cells in tissues from macaques that control viral replication (controllers) and those that have persistently high plasma
viremia (progressors). A positive correlation was detected between tissue RNA+ cells and plasma viral load in both mesenteric lymph node (LN) and spleen. Similarly, a positive correlation also observed between DNA+ cells and plasma viral load in ileum and jejunum. Controllers had a lower frequency of both
RNA and DNA+ cells in several tissues compared to progressors. However, DNA+ cells were prevalent in mesenteric LN, inguinal LN, colon, midbrain, and bone marrow tissues in both controller and progressors. Organized lymphoid tissues of LNs, spleen, and intestine were found as the major tissues positive for virus.
Viral RNA and
DNA positive cells were detected in brain and thymus in macaques with high plasma
viremia and SIV-
encephalitis. Both T cells and macrophages were shown to be infected in several tissues, indicating
vaccines and ART should be specifically designed to protect these cells in organized lymphoid tissues. These results indicate ART should target infected cells in secondary lymphoid organs to reduce both productively and latently infected cells.