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Eur J Immunol. 2004 Jun;34(6):1705-14.

HIV infection of primary human T cells is determined by tunable thresholds of T cell activation.

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Department of Microbiology and Immunology, Vanderbilt University Medical School, Nashville, TN 37232, USA.


HIV infection of primary human T cells requires T cell activation signals. However, how strength, duration, and quality of TCR signals affect susceptibility of resting human T cells to HIV infection remains poorly understood. We found that the same threshold and duration of antigen signals that lead to optimal T cell activation are required for HIV to progress beyond the level of reverse transcription within resting T cells. Remarkably, sustained cytokine signaling from the IL-2 receptor following TCR triggering was critical in establishing productive infection. While blockade of TCR signaling pathways with inhibitors of the phosphatidylinositol 3-kinase pathway caused a partial pre-integration block, another inhibitor, rapamycin, completely suppressed the infection. In contrast, cyclosporin A or FK506, inhibitors of NFAT, failed to block infection if the T cells were pre-activated. Collectively, these results bring to light significant parallels between successful HIV infection and optimal thresholds of T cell activation. Furthermore, our results underscore the critical role of IL-2 signaling in establishing productive HIV infection. These findings have important implications for our understanding of the complex interplay of HIV with host factors induced upon T cell activation.

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