Lee C G, Ramachandra M, Jeang K T, Martin M A, Pastan I, Gottesman M M
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.
FASEB J. 2000 Mar;14(3):516-22. doi: 10.1096/fasebj.14.3.516.
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.
多药耐药蛋白1多药转运体P-糖蛋白(P-糖蛋白)是一种外排泵,可将多种疏水性药物和肽从细胞中排出。由于HIV-1进入细胞涉及病毒gp41疏水肽与质膜的初始相互作用,因此研究了P-糖蛋白对HIV-1感染性的潜在影响。当P-糖蛋白在感染了HIV-1(NL4-3)(一种HIV-1的T嗜性分子克隆)的连续CD4(+)人T白血病细胞系(12D7)表面过度表达时,病毒产生显著减少。P-糖蛋白的过度表达并未显著改变HIV-1受体CD4或共受体CXCR4的表面表达或分布。在表达P-糖蛋白的细胞中,HIV-1感染性的降低发生在病毒膜与质膜融合期间以及HIV-1生命周期的后续步骤中。