Macrophage are the principal reservoir and sustain high virus loads in rhesus macaques after the depletion of CD4(+) T cells by a highly pathogenic simian immunodeficiency virus/HIV type 1 chimera (SHIV): Implications for HIV-1 infections of humans

The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chime ric virus SHIVDH12R induces a systemic depletion of CD4(+) T lymphocytes in rhesus monkeys during the initial 3-4 weeks of infection. Nonetheless, hig h levels of viral RNA production continue unabated for an additional 2-5 mo nths. In situ hybridization and immunohistochemical analyses revealed that tissue macrophage in the lymph nodes, spleen, gastrointestinal tract, liver , and kidney sustain high plasma virus loads in the absence of CD4(+) T cel ls. Quantitative confocal immunofluorescence analysis indicated that greate r than 95% of the virus-producing cells in these tissues are macrophage and less than 2% are T lymphocytes. Interestingly, the administration of a pot ent reverse transcriptase inhibitor blocked virus production during the ear ly T cell phase but not during the later macrophage phase of the SHIVDH12R infection. When interpreted in the context of HIV-1 infections these result s implicate tissue macrophage as an important reservoir of virus in vivo. T hey become infected during the acute infection, gradually increase in numbe r over time, and can be a major contributor to total body virus burden duri ng the symptomatic phase of the human infection.