Reduced cellular susceptibility to in vitro HIV infection is associated with CD4+ T cell quiescence.
Reduced cellular susceptibility to in vitro HIV infection is associated with CD4+ T cell quiescence.
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DOI：
10.1371/journal.pone.0045911
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fowke KR
中科院分区：
文献类型：
--
作者：
Card CM;Rutherford WJ;Ramdahin S;Yao X;Kimani M;Wachihi C;Kimani J;Plummer FA;Ball TB;Fowke KR
HIV 优先在激活的 CD4+ T 细胞中建立生产性感染。由于活化 CD4+ T 细胞的比例因人而异，本研究旨在确定活化 CD4+ T 细胞比例较高的个体是否更容易受到体外 HIV 感染。来自不同捐赠者的未刺激的外周血单核细胞 (PBMC) 在体外接种 HIVML1956。通过培养物上清液的 HIV p24 ELISA 和 HIV p24 的细胞内染色（通过流式细胞术检测）来评估 HIV 复制。还通过流式细胞术评估了基线 T 细胞表型和感染细胞表型。抽血时的离体表型分析表明，T 细胞活化升高和 Tregs 减少与细胞对体外感染的易感性增加有关。此外，受感染的 CD4+ T 细胞群富集了活化细胞。这些数据表明，CD4+ T 细胞静止通过限制激活的靶细胞池，提供了一个不利于 HIV 感染建立的环境。
HIV preferentially establishes productive infection in activated CD4+ T cells. Since proportions of activated CD4+ T cells vary between individuals, this study aimed to determine if individuals with a greater proportion of activated CD4+ T cells would be more susceptible to in vitro HIV infection. Unstimulated peripheral blood mononuclear cells (PBMC) from various donors were inoculated with HIVML1956 in vitro. HIV replication was evaluated by HIV p24 ELISA of culture supernatants and intracellular staining for HIV p24, which was detected by flow cytometry. Baseline T cell phenotypes and infected cell phenotypes were also evaluated by flow cytometry. Ex vivo phenotyping at the time of blood draw showed that elevated T cell activation and reduced Tregs were associated with increased cellular susceptibility to in vitro infection. Furthermore, the infected CD4+ T cell population was enriched for activated cells. These data suggest that CD4+ T cell quiescence provides an environment less conducive to the establishment of HIV infection by limiting the pool of activated target cells.
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