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        生物資訊

        HIV-1病毒庫的分析

        作者:admin 來源:Nature 發(fā)布時間: 2015-01-16 10:47  瀏覽次數(shù):
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        抗逆轉(zhuǎn)錄病毒療法不能治愈HIV-1感染:盡管接受了藥物治療,但大部分患者體內(nèi)仍有大量處于休眠狀態(tài)的這種病毒,即存在病毒庫。

        對從30位被HIV-1感染的患者(他們持續(xù)接受抗逆轉(zhuǎn)錄病毒治療至少兩年時間并且血漿中的HIV-1 RNA一直保持在檢測不到的水平)分離出的免疫細(xì)胞所做的這項(xiàng)研究顯示,這些病毒庫以具有“細(xì)胞毒性T-淋巴細(xì)胞逃避突變”的病毒為主導(dǎo)。

        該發(fā)現(xiàn)表明,治療性疫苗設(shè)計(jì)的未來方向也許需要關(guān)注怎樣提升大范圍的“細(xì)胞毒性T-淋巴細(xì)胞反應(yīng)”。

        原文鏈接:

        Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations

        Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-1 persists in a stable latent reservoir1, 2, primarily in resting memory CD4+ T cells3, 4. This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed5 and tested both in vitro and in vivo6, 7, 8. A key remaining question is whether virus-specific immune mechanisms, including cytotoxic T lymphocytes (CTLs), can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad-spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir.(doi:10.1038/nature14053)

        HIV: Seeking ultimate victory

        HIV variants that have mutated to escape T-cell immune responses dominate the latent viral reservoir in most patients on antiretroviral therapy. This finding will need to guide therapeutic approaches targeting reactivated virus. (doi:10.1038/nature14194)

        對應(yīng)Nature雜志: 2015年01月15日Nature雜志精選

         

         

         

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