Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7

EMBO J. 2003 Jul 15;22(14):3675-85. doi: 10.1093/emboj/cdg357.

Abstract

Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. This property depends on the active nuclear import of its intracellular reverse transcription complex (RTC). We have studied nuclear import of purified HIV-1 RTCs in primary macrophages and found that importin 7, an import receptor for ribosomal proteins and histone H1, is involved in the process. Nuclear import of RTCs requires, in addition, energy and the components of the Ran system. Depletion of importin 7 from cultured cells by small interfering RNA inhibits HIV-1 infection. These results provide a new insight into the molecular mechanism for HIV-1 nuclear import and reveal potential targets for therapeutic intervention.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • CD4 Antigens / metabolism
  • Cell Nucleolus / metabolism
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism*
  • Cell Nucleus / virology
  • Cells, Cultured
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • HIV Infections* / virology
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / metabolism*
  • HeLa Cells
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Macrophages / metabolism
  • Mutation
  • Nuclear Envelope / metabolism
  • RNA, Small Interfering / metabolism
  • Receptors, CCR5 / metabolism
  • Transcription, Genetic
  • ran GTP-Binding Protein / metabolism

Substances

  • CD4 Antigens
  • DNA, Viral
  • Karyopherins
  • RNA, Small Interfering
  • Receptors, CCR5
  • HIV Reverse Transcriptase
  • ran GTP-Binding Protein