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.

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Journal Nature Communications
Lucic, B. (Bojana), Chen, H.-C. (Heng-Chang), Kuzman, M. (Maja), Zorita, E. (Eduard), Wegner, J. (Julia), Minneker, V. (Vera), … Lusic, M. (Marina). (2019). Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration. Nature Communications, 10(1). doi:10.1038/s41467-019-12046-3