Effect of ABC transporters on HIV-1 infection: inhibition of virus production by the MDR1 transporter

(3)The MDR1 multidrug transporter P-gp (P-glycoprotein) is an efflux pump t hat extrudes diverse hydrophobic drugs and peptides from cells. Since the e ntry of HIV-1 into cells involves an initial interaction of the viral gp41 hydrophobic peptide with the plasma membrane, a potential effect of P-gp on HIV-1 infectivity was explored. Virus production was greatly decreased whe n P-gp was overexpressed at the surface of a continuous CD4(+) human T-leuk emic cell line (12D7) infected with HIV-1(NL4-3) a T-tropic molecular clone of HIV-1. P-gp overexpression did not significantly alter the surface expr ession or distribution of either the HIV-1 receptor CD4 or the coreceptor C XCR4. Reduction of HIV-1 infectivity in P-gp-expressing cells occurred both during the fusion of viral and plasma membranes and at subsequent step(s) in the HIV-1 life cycle.