Inhibition of HIV-1 replication by cyclosporine A or related compounds correlates with the ability to disrupt the Gag-cyclophilin A interaction.

Abstract:

:The HIV-1 Gag polyprotein specifically incorporates the cellular peptidylprolyl isomerase cyclophilin A into virions. HIV-1 replication is inhibited by cyclosporine A, an immunosuppressive drug which binds with high affinity to cyclophilin A and precludes interaction with the Gag polyprotein. Using a panel of four drugs, including cyclosporine A, two nonimmunosuppressive analogues of cyclosporine A which bind to cyclophilin A but which cannot form a tertiary complex with the calcium-dependent phosphatase calcineurin, and the structurally unrelated immunosuppressant FK506, we demonstrated that the antiviral effect of cyclosporine A is not due to blockade of calcineurin-mediated signal transduction pathways. Rather, the effectiveness of cyclosporine A and related compounds at inhibiting HIV-1 replication correlates with cyclophilin A-binding affinity and with the ability to disrupt the interaction between cyclophilin A and the HIV-1 Gag polyprotein. These results support the contention that the Gag-cyclophilin A interaction is required for HIV-1 replication.

journal_name

Virology

journal_title

Virology

authors

Franke EK,Luban J

doi

10.1006/viro.1996.0421

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

279-82

issue

1

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(96)90421-3

journal_volume

222

pub_type

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