What Integration Sites Tell Us about HIV Persistence.
What Integration Sites Tell Us about HIV Persistence.
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DOI：
10.1016/j.chom.2016.04.010
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发表时间：
2016-05-11
影响因子：
30.3
通讯作者：
Coffin JM
中科院分区：
文献类型：
--
作者：
Hughes SH;Coffin JM
技术的进步使分析HIV感染者细胞中的整合位点成为可能。在接受长期治疗的患者中，相当一部分感染细胞是克隆性扩增的；在某些情况下，整合的病毒DNA有助于感染细胞的克隆性扩增。尽管在接受治疗的患者中，绝大多数(95%)的HIV前病毒是有缺陷的，但扩大的克隆可以携带具有复制能力的前病毒，来自这些克隆的细胞可以释放传染性病毒。正如在这一视角中所讨论的，产生病毒的细胞很可能是在体内被强烈选择的，具有复制能力的前病毒的细胞扩张并存活下来，因为只有一小部分细胞产生病毒。这些发现对旨在消除使艾滋病毒感染患者几乎不可能治愈的感染细胞储存库的战略具有影响。
Advances in technology have made it possible to analyze integration sites in cells from HIV infected patients. A significant fraction of infected cells in patients on long-term therapy are clonally expanded; in some cases the integrated viral DNA contributes to the clonal expansion of the infected cells. Although the large majority (>95%) of the HIV proviruses in treated patients are defective, expanded clones can carry replication competent proviruses, and cells from these clones can release infectious virus. As discussed in this Perspective, it is likely that cells that produce virus are strongly selected against in vivo, and cells with replication competent proviruses expand and survive because only a small fraction of the cells produce virus. These findings have implications for strategies that are intended to eliminate the reservoir of infected cells that has made it almost impossible to cure HIV infected patients.