Nuclear architecture dictates HIV-1 integration site selection

Long-standing evidence indicates that human immunodeficiency
virus type 1 (HIV-1) preferentially integrates into a subset of
transcriptionally active genes of the host cell genome1–4. However,
the reason why the virus selects only certain genes among all
transcriptionally active regions in a target cell remains largely
unknown. Here we show that HIV-1 integration occurs in the outer
shell of the nucleus in close correspondence with the nuclear pore.
This regioncontains a seriesof cellular genes,which arepreferentially
targeted by the virus, and characterized by the presence of active
transcription chromatin marks before viral infection. In contrast,
the virus strongly disfavours the heterochromatic regions in the
nuclear lamin-associateddomains5 and other transcriptionally active
regions located centrally in the nucleus. Functional viral integrase
and the presence of the cellularNup153 and LEDGF/p75 integration
cofactors are indispensable for the peripheral integration of the
virus. Once integrated at the nuclear pore, the HIV-1 DNA makes
contact with various nucleoporins; this association takes part in the
transcriptional regulation of the viral genome.These results indicate
that nuclear topography is an essential determinant of the HIV-1
life cycle.