HIV-1 nuclear import in macrophages is regulated by CPSF6-capsid interactions at the nuclear pore complex

Elife. 2019 Jan 23;8:e41800. doi: 10.7554/eLife.41800.


Nuclear entry of HIV-1 replication complexes through intact nuclear pore complexes is critical for successful infection. The host protein cleavage-and-polyadenylation-specificity-factor-6 (CPSF6) has been implicated in different stages of early HIV-1 replication. Applying quantitative microscopy of HIV-1 reverse-transcription and pre-integration-complexes (RTC/PIC), we show that CPSF6 is strongly recruited to nuclear replication complexes but absent from cytoplasmic RTC/PIC in primary human macrophages. Depletion of CPSF6 or lack of CPSF6 binding led to accumulation of HIV-1 subviral complexes at the nuclear envelope of macrophages and reduced infectivity. Two-color stimulated-emission-depletion microscopy indicated that under these circumstances HIV-1 complexes are retained inside the nuclear pore and undergo CA-multimer dependent CPSF6 clustering adjacent to the nuclear basket. We propose that nuclear entry of HIV-1 subviral complexes in macrophages is mediated by consecutive binding of Nup153 and CPSF6 to the hexameric CA lattice.

Keywords: CPSF6; Human immunodeficiency virus; cell biology; human; infectious disease; macrophages; microbiology; nuclear import; nuclear pore complex; pre-integration complex; virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Capsid / drug effects
  • Capsid / metabolism*
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism*
  • HIV-1 / drug effects
  • HIV-1 / metabolism*
  • HIV-1 / pathogenicity
  • HeLa Cells
  • Humans
  • Indoles / pharmacology
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Macrophages / virology*
  • Nuclear Pore Complex Proteins / metabolism*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Virus Internalization / drug effects
  • Virus Replication / drug effects
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Indoles
  • Intercellular Signaling Peptides and Proteins
  • NUP153 protein, human
  • Nuclear Pore Complex Proteins
  • PF-3450074
  • cleavage factor Im, human
  • lens epithelium-derived growth factor
  • mRNA Cleavage and Polyadenylation Factors
  • Phenylalanine