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

ABSTRACT 3 The MDR1 multidrug transporter P‐gp (P‐glycoprotein) is an efflux pump that extrudes diverse hydrophobic drugs and peptides from cells. Since the entry 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 when P‐gp was overexpressed at the surface of a continuous CD4 + human T‐leukemic 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 expression or distribution of either the HIV‐1 receptor CD4 or the coreceptor CXCR4. 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.—Lee, C. G. L., Ramachandra, M., Jeang, K.‐T., Martin, M. A., Pastan, I., Gottesman, M. M. Effect of ABC transporters on HIV‐1 infection: inhibition of virus production by the MDR1 transporter. FASEB J. 14, 516–522 (2000)