Inhibitory Control of HIV-1 by Cyclophilin A

Abstract

The host protein cyclophilin A (CypA) can both stimulate and inhibit HIV-1 infection through its interaction with the viral capsid (CA). CypA enhances the early stages of HIV-1 infection in part by promoting nuclear import of the virus; while the details of its ability to inhibit HIV-1 infection are less clear. This thesis advances our understanding of the mechanisms underlying the ability of CypA to inhibit HIV-1 infection. I demonstrate that CypA inhibits nuclear import of HIV-1 in the presence of inhibitory capsid-binding host proteins TRIM5α and CPSF6, and that inhibition is not a consequence of increased binding of inhibitory factors to the viral capsid. My work also demonstrates that CypA-dependent inhibition depends in part, on a conserved domain of HIV-1 CA which determines interactions with host nuclear pore proteins. These results suggest a common mechanism underlies the ability of CypA to stimulate HIV-1 infectivity in some cells and to inhibit infection in others.