Spatially clustered loci with multiple enhancers are frequent targets of HIV-1 integration

Bojana Lucic, Heng-Chang Chen, Maja Kuzman, Eduard Zorita, Julia Wegner, Vera Minneker, Wei Wang, Raffaele Fronza, Stefanie Laufs, Manfred Schmidt, Ralph Stadhouders, Vassilis Roukos, Kristian Vlahovicek (), Guillaume J. Filion () and Marina Lusic ()
Additional contact information
Bojana Lucic: Heidelberg University Hospital and German Center for Infection Research
Heng-Chang Chen: Barcelona Institute of Science and Technology
Maja Kuzman: University of Zagreb
Eduard Zorita: Barcelona Institute of Science and Technology
Julia Wegner: Heidelberg University Hospital and German Center for Infection Research
Vera Minneker: Institute of Molecular Biology (IMB)
Wei Wang: German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
Raffaele Fronza: German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
Stefanie Laufs: German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
Manfred Schmidt: German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
Ralph Stadhouders: Erasmus MC
Vassilis Roukos: Institute of Molecular Biology (IMB)
Kristian Vlahovicek: University of Zagreb
Guillaume J. Filion: Barcelona Institute of Science and Technology
Marina Lusic: Heidelberg University Hospital and German Center for Infection Research

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12046-3

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