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

CAROLINE G. L. LEE^*,1, MURALIDHARA RAMACHANDRA^,2, KUAN-TEH JEANG, MALCOLM A. MARTIN, IRA PASTAN² and MICHAEL M. GOTTESMAN^*3

^* Laboratory of Cell Biology,
Laboratory of Molecular Biology, National Cancer Institute,
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

³Correspondence: Laboratory of Cell Biology, Building 37, Room 1A09, National Cancer Institute, National Institutes of Health, 37 Convent Drive MSC 4255, Bethesda, MD 20892-4255, USA. E-mail: mgottesman{at}nih.gov

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.

Key Words: ABC transporters • acquired immunodeficiency syndrome • AIDS • P-glycoprotein • virus entry

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