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.
复制标题
巨噬细胞是恒河猴的主要储存库，在高致病性猿猴免疫缺陷病毒/HIV 1 型嵌合体 (SHIV) 耗尽 CD4 T 细胞后维持恒河猴的高病毒载量：对人类 HIV-1 感染的影响。
DOI：
10.1073/pnas.98.2.658
复制
发表时间：
2001
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;Endo,Y;Buckler-White,A;Plishka,R;Bischofberger,N;Hirsch,V;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。原位杂交和免疫组织化学分析显示，在没有CD 4 +T细胞的情况下，淋巴结、脾脏、胃肠道、肝脏和肾脏中的组织巨噬细胞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细胞阶段阻断病毒产生，但在晚期巨噬细胞阶段不阻断病毒产生。当解释在HIV-1感染的背景下，这些结果暗示组织巨噬细胞作为体内病毒的重要水库。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 SHIVDH12Rinduces 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 situhybridization 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 SHIVDH12Rinfection. When interpreted in the context of HIV-1 infections, these results implicate tissue macrophage as an important reservoir of virusin 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.