HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.

HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells.
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艾滋病毒潜伏期。特定的HIV整合位点与受感染细胞的克隆扩张和持久性有关。

DOI:
10.1126/science.1254194
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发表时间:
2014-07-11
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Hughes SH
Hughes SH
中科院分区:
其他
文献类型:
--
作者:
Maldarelli F;Wu X;Su L;Simonetti FR;Shao W;Hill S;Spindler J;Ferris AL;Mellors JW;Kearney MF;Coffin JM;Hughes SH

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在接受抑制性联合抗逆转录病毒疗法(CART)的个体中,艾滋病毒感染细胞的持久性是治愈艾滋病毒感染的主要障碍。HIV将其DNA整合到宿主基因组的多个位置;我们在CART上的五个感染者的外周血淋巴细胞中鉴定了2410个整合位点。大约40%的整合是在克隆扩增的细胞中进行的。在一名患者中,大约50%的感染细胞来自单个克隆,有些克隆持续了多年。在包括MKL2和BACH2在内的几个基因中有多个独立的整合;这些整合中的许多都是在克隆扩增的细胞中进行的。我们的发现表明,HIV整合位点可以在HIV感染细胞的扩增和持久性方面发挥关键作用。
The persistence of HIV-Infected cells in individuals on suppressive combination antiretroviral therapy (cART) presents a major barrier for curing HIV infections. HIV integrates its DNA into many sites in the host genome; we identified 2410 integration sites in peripheral blood lymphocytes of five infected individuals on cART. About 40% of the integrations were in clonally expanded cells. Approximately 50% of the infected cells in one patient were from a single clone and some clones persisted for many years. There were multiple independent integrations in several genes, including MKL2 and BACH2; many of these integrations were in clonally expanded cells. Our findings show that HIV integration sites can play a critical role in expansion and persistence of HIV infected cells.
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