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Estradiol and Progesterone Regulate HIV Type 1 Replication in Peripheral Blood Cells

机译：雌二醇和孕酮调节周围血细胞中的HIV 1型复制

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Endogenous levels of estradiol and progesterone fluctuate in the peripheral blood of premenopausal women during the reproductive cycle. We studied the effects of these sex hormones on HIV-1 replication in peripheral blood mononuclear cells (PBMCs). We compared HIV-1 replication in PBMCs infected in the presence of mid-secretory (high concentrations) and mid-proliferative (low concentrations) or in the absence of sex hormones. With PBMCs from men, we used concentrations of estradiol and progesterone that are normally present in their plasma. Our findings demonstrate that mid-proliferative phase conditions increased, and mid-secretory phase conditions decreased, HIV-1 replication. To determine if sex hormones affect specific stages of the viral life cycle we performed real-time PCR assays and found decreased levels of HIV-1 integration in the mid-secretory phase and increased levels viral transcription in the mid-proliferative phase. No significant effects on HIV-1 reverse transcription or on CCR5 expression were found. In addition, we assessed hormonal regulation of the HIV-1 LTR in the absence of the viral regulatory protein Tat. We observed that mid-proliferative hormone levels enhanced, whereas mid-secretory hormone concentrations reduced, the activity of the LTR. These findings demonstrate that in HIV-1-infected cells, estradiol and progesterone regulate HIV-1 replication most likely by directly altering HIV-1 transcriptional activation. An additional indirect mechanism of sex hormone regulation of cytokine and chemokine secretion cannot be excluded.
机译：绝经前妇女在生殖周期中内源性雌二醇和孕酮的水平波动。我们研究了这些性激素对外周血单核细胞（PBMC）中HIV-1复制的影响。我们比较了在分泌中期（高浓度）和增殖中期（低浓度）或无性激素感染的PBMC中HIV-1的复制情况。对于男性的PBMC，我们使用了血浆中通常存在的雌二醇和孕酮浓度。我们的发现表明，增生中期条件增加，而分泌中期条件减少，HIV-1复制。为了确定性激素是否影响病毒生命周期的特定阶段，我们进行了实时PCR分析，发现在分泌中期，HIV-1整合水平下降，在增殖中期，病毒转录水平上升。没有发现对HIV-1逆转录或CCR5表达有明显影响。另外，我们在缺乏病毒调节蛋白Tat的情况下评估了HIV-1 LTR的激素调节。我们观察到中期增殖激素水平升高，而分泌中期激素浓度降低，LTR的活性。这些发现表明，在感染了HIV-1的细胞中，雌二醇和孕酮最有可能通过直接改变HIV-1的转录激活来调节HIV-1的复制。不能排除性激素调节细胞因子和趋化因子分泌的其他间接机制。

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