Capsid-CPSF6 Interaction Licenses Nuclear HIV-1 Trafficking to Sites of Viral DNA Integration

Cell Host Microbe. 2018 Sep 12;24(3):392-404.e8. doi: 10.1016/j.chom.2018.08.002. Epub 2018 Aug 30.


HIV-1 integration into the host genome favors actively transcribed genes. Prior work indicated that the nuclear periphery provides the architectural basis for integration site selection, with viral capsid-binding host cofactor CPSF6 and viral integrase-binding cofactor LEDGF/p75 contributing to selection of individual sites. Here, by investigating the early phase of infection, we determine that HIV-1 traffics throughout the nucleus for integration. CPSF6-capsid interactions allow the virus to bypass peripheral heterochromatin and penetrate the nuclear structure for integration. Loss of interaction with CPSF6 dramatically alters virus localization toward the nuclear periphery and integration into transcriptionally repressed lamina-associated heterochromatin, while loss of LEDGF/p75 does not significantly affect intranuclear HIV-1 localization. Thus, CPSF6 serves as a master regulator of HIV-1 intranuclear localization by trafficking viral preintegration complexes away from heterochromatin at the periphery toward gene-dense chromosomal regions within the nuclear interior.

Keywords: CPSF6; HIV capsid; HIV integrase; HIV integration; HIV trafficking; LEDGF/p75; lamina-associated domain; nuclear trafficking.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology*
  • DNA, Viral / genetics*
  • DNA, Viral / metabolism
  • HIV Infections / genetics
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / physiology*
  • Host-Pathogen Interactions
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Protein Binding
  • Virus Integration*
  • Virus Replication
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • DNA, Viral
  • Intercellular Signaling Peptides and Proteins
  • cleavage factor Im, human
  • lens epithelium-derived growth factor
  • mRNA Cleavage and Polyadenylation Factors