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

被引:307
作者
Igarashi, T
Brown, CR
Endo, Y
Buckler-White, A
Plishka, R
Bischofberger, N
Hirsch, V
Martin, MA [1 ]
机构
[1] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA
[2] Gilead Sci Inc, Foster City, CA 94404 USA
关键词
D O I
10.1073/pnas.021551798
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:658 / 663
页数:6
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