Effect of ABC transporters on HIV-1 infection: inhibition of virus production by the MDR1 transporter.
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
CG
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.
Ramachandra
M
M
Jeang
K T
KT
Martin
M A
MA
Pastan
I
I
Gottesman
M M
MM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D019943:Amino Acid Substitution; D015704:CD4 Antigens / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes; D005434:Flow Cytometry; D019450:Genes, MDR; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015458:Leukemia, T-Cell; D008018:Life Cycle Stages; D017354:Point Mutation; D019718:Receptors, CXCR4 / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014779:Virus Replication
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41; D019718:Receptors, CXCR4