Unknown

Dataset Information

0

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


ABSTRACT: 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.

PROVIDER: S-EPMC145517 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC3033441 | BioStudies
| S-EPMC7119052 | BioStudies
2008-01-01 | S-EPMC2440657 | BioStudies
| S-EPMC3234246 | BioStudies
2011-01-01 | S-EPMC3141903 | BioStudies
| S-EPMC3311600 | BioStudies
1996-01-01 | S-EPMC190352 | BioStudies
| S-EPMC7114444 | BioStudies
| S-EPMC5049736 | BioStudies
| S-EPMC4942341 | BioStudies