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 …

T Igarashi, CR Brown, Y Endo… - Proceedings of the …, 2001 - National Acad Sciences
T Igarashi, CR Brown, Y Endo, A Buckler-White, R Plishka, N Bischofberger, V Hirsch…
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus
SHIVDH12R induces a systemic depletion of CD4+ T lymphocytes in rhesus monkeys
during the initial 3–4 weeks of infection. Nonetheless, 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 …
The highly pathogenic simian immunodeficiency virus/HIV type 1 (SHIV) chimeric virus SHIVDH12R induces a systemic depletion of CD4+ T lymphocytes in rhesus monkeys during the initial 3–4 weeks of infection. Nonetheless, 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% of the virus-producing cells in these tissues are macrophage and less than 2% 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 SHIVDH12R infection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage 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.
National Acad Sciences