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Virology. 1996 Aug 1;222(1):279-82.

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

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Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.


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.

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