Department of Infectious Diseases, Integrative Virology, Heidelberg University Hospital and German Center for Infection Research, Heidelberg, Germany.
Genome Architecture, Gene Regulation, Stem Cells and Cancer Programme, Center for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain.
Nat Commun. 2019 Sep 6;10(1):4059. doi: 10.1038/s41467-019-12046-3.
HIV-1 recurrently targets active genes and integrates in the proximity of the nuclear pore compartment in CD4 T cells. However, the genomic features of these genes and the relevance of their transcriptional activity for HIV-1 integration have so far remained unclear. Here we show that recurrently targeted genes are proximal to super-enhancer genomic elements and that they cluster in specific spatial compartments of the T cell nucleus. We further show that these gene clusters acquire their location during the activation of T cells. The clustering of these genes along with their transcriptional activity are the major determinants of HIV-1 integration in T cells. Our results provide evidence of the relevance of the spatial compartmentalization of the genome for HIV-1 integration, thus further strengthening the role of nuclear architecture in viral infection.
HIV-1 经常靶向活性基因，并在 CD4 T 细胞的核孔附近整合。然而，这些基因的基因组特征及其转录活性与 HIV-1 整合的相关性迄今仍不清楚。在这里，我们表明，经常靶向的基因靠近超级增强子基因组元件，并且它们在 T 细胞核的特定空间隔室中聚集。我们进一步表明，这些基因簇在 T 细胞的激活过程中获得其位置。这些基因的聚类及其转录活性是 HIV-1 在 T 细胞中整合的主要决定因素。我们的研究结果为基因组空间分隔与 HIV-1 整合的相关性提供了证据，从而进一步加强了核结构在病毒感染中的作用。
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