HIV-1 'preferentially' integrates into a subset of transcriptionally active host genes, but how some of these genes are selected remains unclear. In Nature, Marini et al. show that HIV-1 DNA integration occurs in genes located near the outer shell of the nucleus that are marked by active transcription chromatin marks and are proximal to the nuclear pore. The identification of genes that undergo recurrent HIV-1 integration and mapping them in the nuclear architecture or the direct visualization of HIV-1-integration sites in CD4+ T cells shows 'preferential' localization of viral DNA next to the nuclear envelope. In contrast, the virus 'disfavors' heterochromatic regions in the nuclear periphery or more centrally located transcriptionally active regions. Once integrated, the HIV-1 DNA makes contact with subunits of the nuclear pore complex called nucleoporins; silencing of several nucleoporins diminishes HIV-1's transcriptional activity. These observations suggest that HIV-1 DNA integrates in the first open chromatin regions encountered in the nucleus, which might be related to the short lifetime of the viral integrase.

Nature (2 March 2015) doi:10.1038/nature14226