Simian immunodeficiency virus replicates to high levels in naturally infected African green monkeys without inducing immunologic or neurologic disease

African green monkeys can maintain long-term persistent infection with simi an immunodeficiency viruses (SIVagm) without developing AIDS and thus provi de an important model for understanding mechanisms of natural host resistan ce to disease. This study assessed the levels and anatomic distribution of SIVagm in healthy, naturally infected monkeys. Quantitative competitive rev erse transcriptase PCR assays developed to measure SIVagm from two African green monkey subspecies demonstrated high levels of SIV RNA in plasma (>6 x 10(6) RNA copies/ml) in sabaeus and vervet monkeys. Infectious virus was r eadily recovered from plasma and peripheral blood mononuclear cells and sho wn to be highly cytopathic in human cell lines and macrophages. SIVagm DNA levels were highest in the gastrointestinal tract, suggesting that the gut is a major site for SIVagm replication in vivo. Appreciable levels of virus were also found within the brain parenchyma and the cerebrospinal fluid (C SF), with lower levels detected in peripheral blood cells and lymph nodes. Virus isolates from the CSF and brain parenchyma readily infected macrophag es in culture, whereas lymph node isolates were more restricted to growth i n human T-cell lines. Comparison of env V2-C4 sequences showed extensive am ino acid diversity between SIVagm recovered from the central nervous system and that recovered from lymphoid tissues. Homology between brain and CSF v iruses, macrophage tropism, and active replication suggest compartmentaliza tion in the central nervous system without associated neuropathology in nat urally infected monkeys. These studies provide evidence that the nonpathoge nic nature of SIVagm in the natural host can be attributed neither to more effective host control over viral replication nor to differences in the tis sue and cell tropism from those for human immunodeficiency virus type 1-inf ected humans or SIV-infected macaques.