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

摘要

The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIV_DH12R induces a systemic depletion of CD4~+ T lymphocytes in rhesus monkeys during the initial 3--4 weeks of infection. Nonatheless, high levels of viral RNA production continue unabated for an additional 2--5 months. 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 cells. Quantitative confocal immunofluorescence analysis indicated that greater than 95/100 of the virus-producing cells in these tissues are macrophage and less than 2/100 are T lymphocytes. Interestingly, the administration of a potent reverse transcriptase inhibitor blocked virus production during the early T cell phase but not during the later macrophage phase of the SHIV_DH12R infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macro- phage as an important reservoir of virus in vivo. They become infected during the acute infection, gradually increase in number over time, and can be a major contributor to total body virus burden during the symptomatic phase of the human infection.