Cyclophilin A regulates HIV-1 infectivity, as demonstrated by gene targeting in human T cells

EMBO J. 2001 Mar 15;20(6):1300-9. doi: 10.1093/emboj/20.6.1300.


The human immunodeficiency virus type 1 (HIV-1) Gag polyprotein binds most members of the cyclophilin family of peptidyl-prolyl isomerases. Of 15 known human cyclophilins, cyclophilin A (CypA) has been the focus of investigation because it was detected in HIV-1 virions. To determine whether CypA promotes HIV-1 replication, we deleted the gene encoding CypA (PPIA) in human CD4(+) T cells by homologous recombination. HIV-1 replication in PPIA(-/-) cells was decreased and not inhibited further by cyclosporin or gag mutations that disrupt Gag's interaction with cyclophilins, indicating that no other cyclophilin family members promote HIV-1 replication. The defective replication phenotype was specific for wild-type HIV-1 since HIV-2/SIV isolates, as well as HIV-1 bearing a gag mutation that confers cyclosporin resistance, replicated the same in PPIA(+/+) and PPIA(-/-) cells. Stable re-expression of CypA in PPIA(-/-) cells restored HIV-1 replication to an extent that correlated with steady-state levels of CypA. Finally, virions from PPIA(-/-) cells possessed no obvious biochemical abnormalities but were less infectious than virions from wild-type cells. These data formally demonstrate that CypA regulates the infectivity of HIV-1 virions.

Publication types

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

MeSH terms

  • Cell Survival
  • Cyclophilin A / genetics
  • Cyclophilin A / metabolism
  • Cyclophilin A / pharmacology*
  • Gene Products, gag / metabolism
  • Gene Targeting
  • HIV-1 / drug effects*
  • HIV-1 / growth & development
  • HIV-1 / pathogenicity*
  • Humans
  • Jurkat Cells
  • Mutagenesis
  • Recombination, Genetic
  • T-Lymphocytes / cytology
  • T-Lymphocytes / virology*
  • Virus Replication / drug effects


  • Gene Products, gag
  • Cyclophilin A