HIV-1 replication complexes accumulate in nuclear speckles and integrate into speckle-associated genomic domains

Nat Commun. 2020 Jul 14;11(1):3505. doi: 10.1038/s41467-020-17256-8.


The early steps of HIV-1 infection, such as uncoating, reverse transcription, nuclear import, and transport to integration sites are incompletely understood. Here, we imaged nuclear entry and transport of HIV-1 replication complexes in cell lines, primary monocyte-derived macrophages (MDMs) and CD4+ T cells. We show that viral replication complexes traffic to and accumulate within nuclear speckles and that these steps precede the completion of viral DNA synthesis. HIV-1 transport to nuclear speckles is dependent on the interaction of the capsid proteins with host cleavage and polyadenylation specificity factor 6 (CPSF6), which is also required to stabilize the association of the viral replication complexes with nuclear speckles. Importantly, integration site analyses reveal a strong preference for HIV-1 to integrate into speckle-associated genomic domains. Collectively, our results demonstrate that nuclear speckles provide an architectural basis for nuclear homing of HIV-1 replication complexes and subsequent integration into associated genomic loci.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • CD4-Positive T-Lymphocytes / metabolism
  • Capsid Proteins / genetics
  • Capsid Proteins / metabolism
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Genome, Viral / genetics
  • HEK293 Cells
  • HIV Infections / genetics
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / physiology
  • Humans
  • Microscopy, Fluorescence
  • Virology
  • Virus Integration / genetics
  • Virus Integration / physiology
  • Virus Replication / genetics
  • Virus Replication / physiology


  • Capsid Proteins