潜伏感染和活跃感染期间的HIV-1整合图谱。
HIV-1 integration landscape during latent and active infection.
作者信息
Cohn Lillian B, Silva Israel T, Oliveira Thiago Y, Rosales Rafael A, Parrish Erica H, Learn Gerald H, Hahn Beatrice H, Czartoski Julie L, McElrath M Juliana, Lehmann Clara, Klein Florian, Caskey Marina, Walker Bruce D, Siliciano Janet D, Siliciano Robert F, Jankovic Mila, Nussenzweig Michel C
机构信息
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; National Institute of Science and Technology in Stem Cell and Cell Therapy and Center for Cell Based Therapy, Rua Catão Roxo, 2501, Ribeirão Preto CEP 14051-140, Brazil.
出版信息
Cell. 2015 Jan 29;160(3):420-32. doi: 10.1016/j.cell.2015.01.020.
The barrier to curing HIV-1 is thought to reside primarily in CD4(+) T cells containing silent proviruses. To characterize these latently infected cells, we studied the integration profile of HIV-1 in viremic progressors, individuals receiving antiretroviral therapy, and viremic controllers. Clonally expanded T cells represented the majority of all integrations and increased during therapy. However, none of the 75 expanded T cell clones assayed contained intact virus. In contrast, the cells bearing single integration events decreased in frequency over time on therapy, and the surviving cells were enriched for HIV-1 integration in silent regions of the genome. Finally, there was a strong preference for integration into, or in close proximity to, Alu repeats, which were also enriched in local hotspots for integration. The data indicate that dividing clonally expanded T cells contain defective proviruses and that the replication-competent reservoir is primarily found in CD4(+) T cells that remain relatively quiescent.
治愈HIV-1的障碍被认为主要存在于含有沉默前病毒的CD4(+) T细胞中。为了表征这些潜伏感染的细胞，我们研究了HIV-1在病毒血症进展者、接受抗逆转录病毒治疗的个体以及病毒血症控制者中的整合情况。克隆扩增的T细胞占所有整合的大部分，且在治疗期间有所增加。然而，所检测的75个扩增T细胞克隆中均未包含完整病毒。相反，带有单个整合事件的细胞在治疗过程中频率随时间下降，存活细胞在基因组的沉默区域富集了HIV-1整合。最后，整合强烈偏好于Alu重复序列或其附近，这些区域在局部整合热点中也很富集。数据表明，克隆扩增的分裂T细胞含有缺陷前病毒，而具有复制能力的病毒库主要存在于相对静止的CD4(+) T细胞中。
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