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
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
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DOI：
10.1073/pnas.021551798
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发表时间：
2001-01-16
影响因子：
11.1
通讯作者：
Martin, MA
中科院分区：
文献类型：
--
作者：
Igarashi, T;Brown, CR;Martin, MA
高致病性猴免疫缺陷病毒/HIV 1型（SHIV）嵌合病毒SHIVDH 12 R在感染的最初3-4周内诱导恒河猴全身性CD 4（+）T淋巴细胞耗竭。尽管如此，高水平的病毒RNA产生持续2-5个月。原位杂交和免疫组织化学分析显示，在淋巴结、脾、胃肠道、肝和肾中的组织巨噬细胞在没有CD 4（+）T细胞的情况下维持高血浆病毒载量。定量共聚焦免疫荧光分析表明，这些组织中超过95%的病毒产生细胞是巨噬细胞，不到2%是T淋巴细胞。有趣的是，施用有效的逆转录酶抑制剂在SHIVDH 12 R感染的早期T细胞阶段阻断了病毒产生，但在晚期巨噬细胞阶段没有阻断。当在HIV-1感染的背景下解释时，这些结果暗示组织巨噬细胞是体内病毒的重要储存库。它们在急性感染期间被感染，随着时间的推移数量逐渐增加，并且在人类感染的症状阶段期间可能是全身病毒负荷的主要贡献者。
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.