Specific incorporation of cyclophilin A into HIV-1 virions

Nature. 1994 Nov 24;372(6504):359-62. doi: 10.1038/372359a0.


Little is known about host factors necessary for retroviral virion assembly or uncoating. We have previously shown that the principal structural protein of the human immunodeficiency virus HIV-1, the Gag polyprotein, binds the cyclophilin peptidyl-prolyl isomerases; cyclophilins catalyse a rate-limiting step in protein folding and protect cells from heat shock. Here we demonstrate that cyclophilin A is specifically incorporated into HIV-1 virions but not into virions of other primate immunodeficiency viruses. A proline-rich region conserved in all HIV-1 Gag polyproteins is required for cyclophilin A binding and incorporation. Disruption of a single proline blocks the Gag-cyclophilin interaction in vitro, prevents cyclophilin A incorporation into virions, and inhibits HIV-1 replication. Our results indicate that the interaction of Gag with cyclophilin A is necessary for the formation of infectious HIV-1 virions.

Publication types

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

MeSH terms

  • Amino Acid Isomerases / metabolism*
  • Amino Acid Sequence
  • Base Sequence
  • Carrier Proteins / metabolism*
  • Cell Line
  • Gene Products, gag / genetics
  • Gene Products, gag / metabolism
  • HIV-1 / metabolism*
  • HIV-1 / physiology
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Oligodeoxyribonucleotides
  • Peptidylprolyl Isomerase
  • Simian Immunodeficiency Virus / metabolism
  • Transfection
  • Virion / metabolism*
  • Virus Replication


  • Carrier Proteins
  • Gene Products, gag
  • Oligodeoxyribonucleotides
  • Amino Acid Isomerases
  • Peptidylprolyl Isomerase