Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors
Author: ["Greg J Towers","Theodora Hatziioannou","Simone Cowan","Stephen P Goff","Jeremy Luban","Paul D Bieniasz"]
Publication: Nature Medicine
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Abstract
Many mammalian species express restriction factors that confer host resistance to retroviral infection. Here we show that HIV-1 sensitivity to restriction factors is modulated by cyclophilin A (CypA), a host cell protein that binds the HIV-1 capsid protein (CA). In certain nonhuman primate cells, the CA–CypA interaction is essential for restriction: HIV-1 infectivity is increased >100-fold by cyclosporin A (CsA), a competitive inhibitor of the interaction, or by an HIV-1 CA mutation that disrupts CypA binding. Conversely, disruption of CA–CypA interaction in human cells reveals that CypA protects HIV-1 from the Ref-1 restriction factor. These findings suggest that HIV-1 has co-opted a host cell protein to counteract restriction factors expressed by human cells and that this adaptation can confer sensitivity to restriction in unnatural hosts. Manipulation of HIV-1 CA recognition by restriction factors promises to advance animal models and new therapeutic strategies for HIV-1 and AIDS.
Cite this article
Towers, G., Hatziioannou, T., Cowan, S. et al. Cyclophilin A modulates the sensitivity of HIV-1 to host restriction factors. Nat Med 9, 1138–1143 (2003). https://doi.org/10.1038/nm910
