Heat-shock protein 70 can replace viral protein R of HIV-1 during nuclear import of the viral preintegration complex

Exp Cell Res. 2000 Sep 15;259(2):398-403. doi: 10.1006/excr.2000.4992.


Heat-shock proteins (Hsp's) are a family of molecular chaperones that contribute to protection from environmental stress. In this report, we demonstrate that a member of this family, Hsp70, facilitates nuclear import of HIV-1 preintegration complexes (PICs). The mechanism of this activity appears to be similar to the one used by Vpr, an HIV-1 protein regulating viral nuclear import and replication in macrophages. Indeed Hsp70 stimulated binding of HIV-1 matrix antigen to GST-karyopherin alpha fusion protein and rescued nuclear import of a Vpr-defective HIV-1 strain in vitro. Binding studies with truncated forms of GST-karyopherin alpha demonstrated that both Vpr and Hsp70 bind to a region in the amino-terminal part of the karyopherin alpha molecule. This region appears to be distinct from the binding sites for two other karyopherin alpha cargoes, basic-type NLS-containing proteins and transcription factor STAT-1. Vpr competed with Hsp70 for binding to karyopherin alpha. These results suggest the presence of a novel regulatory site on karyopherin alpha which is used by Hsp70 and Vpr to stimulate interaction between the HIV-1 PIC and karyopherin alpha and thus promote viral nuclear import.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Polyomavirus Transforming / metabolism
  • Binding Sites / physiology
  • Binding, Competitive / physiology
  • Biological Transport
  • Cell Nucleus / metabolism
  • Cell Nucleus / virology
  • Cytosol / metabolism
  • Cytosol / virology
  • DNA-Binding Proteins / metabolism
  • Gene Products, vpr / genetics
  • Gene Products, vpr / metabolism*
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / growth & development
  • HIV-1 / metabolism*
  • HSP70 Heat-Shock Proteins / metabolism*
  • HeLa Cells
  • Humans
  • Kidney / cytology
  • Mutagenesis / physiology
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • STAT1 Transcription Factor
  • Trans-Activators / metabolism
  • Virus Integration / physiology*
  • Virus Replication
  • alpha Karyopherins
  • vpr Gene Products, Human Immunodeficiency Virus


  • Antigens, Polyomavirus Transforming
  • DNA-Binding Proteins
  • Gene Products, vpr
  • HSP70 Heat-Shock Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Trans-Activators
  • alpha Karyopherins
  • vpr Gene Products, Human Immunodeficiency Virus