Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, and.
Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
JCI Insight. 2021 May 10;6(9):143940. doi: 10.1172/jci.insight.143940.
HIV-1 is capable of integrating its genome into that of its host cell. We examined the influence of the activation state of CD4+ T cells, the effect of antiretroviral therapy (ART), and the clinical stage of HIV-1 infection on HIV-1 integration site features and selection. HIV-1 integration sites were sequenced from longitudinally sampled resting and activated CD4+ T cells from 12 HIV-1-infected individuals. In total, 589 unique HIV-1 integration sites were analyzed: 147, 391, and 51 during primary, chronic, and late presentation of HIV-1 infection, respectively. As early as during primary HIV-1 infection and independent of the activation state of CD4+ T cells collected on and off ART, HIV-1 integration sites were preferentially detected in recurrent integration genes, genes associated with clonal expansion of latently HIV-1-infected CD4+ T cells, cancer-related genes, and highly expressed genes. The preference for cancer-related genes was more pronounced at late stages of HIV-1 infection. Host genomic features of HIV-1 integration site selection remained stable during HIV-1 infection in both resting and activated CD4+ T cells. In summary, characteristic HIV-1 integration site features are preestablished as early as during primary HIV-1 infection and are found in both resting and activated CD4+ T cells.
HIV-1 能够将其基因组整合到宿主细胞的基因组中。我们研究了 CD4+T 细胞的激活状态、抗逆转录病毒治疗（ART）的效果以及 HIV-1 感染的临床阶段对 HIV-1 整合部位特征和选择的影响。我们对 12 名 HIV-1 感染者的静息和激活 CD4+T 细胞进行了纵向采样，并对 HIV-1 整合部位进行了测序。总共分析了 589 个独特的 HIV-1 整合部位：分别在 HIV-1 感染的原发性、慢性期和晚期获得了 147、391 和 51 个整合部位。早在原发性 HIV-1 感染期间，无论 CD4+T 细胞是否在 ART 上下激活，HIV-1 整合部位都优先在反复整合基因、与潜伏 HIV-1 感染的 CD4+T 细胞克隆扩增相关的基因、癌症相关基因和高表达基因中检测到。在 HIV-1 感染的晚期，癌症相关基因的偏好更为明显。在 HIV-1 感染期间，在静息和激活的 CD4+T 细胞中，HIV-1 整合部位选择的宿主基因组特征保持稳定。总之，特征性的 HIV-1 整合部位特征早在原发性 HIV-1 感染期间就已预先建立，并且在静息和激活的 CD4+T 细胞中都存在。
