P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane.
The multidrug resistance gene product P-glycoprotein confers drug resistance to tumor cells by acting as a transporter that blocks the entry into the cell of a great variety of drugs and hydrophobic peptides. In this study we find that in drug-resistant cells, the insertion of the influenza virus fusion protein (hemagglutinin-2) into the plasma membrane is blocked and that the fusion of the viral envelope with the plasma membrane of these cells is impaired. Multidrug-resistant cells display significant resistance to infection by envelope viruses that invade cells by fusion with the plasma membrane, but not to infection by pH-dependent viruses that penetrate cells by fusion with endocytic vesicles. These observations suggest that multidrug resistance phenomena may protect cells from infection by a large group of disease-causing viruses that includes human immunodeficiency virus, herpes simplex virus, and some cancer-inducing retroviruses.
Raviv
Y
Y
Intramural Research Support Program SAIC Frederick, Laboratory of Experimental and Computational Biology, National Cancer Institute, Frederick, MD 21702, USA. yraviv@mail.ncifcrf.gov
Puri
A
A
Blumenthal
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology / Q000821:virology; D018432:Drug Resistance, Multiple; D004705:Endocytosis; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007624:KB Cells; D008561:Membrane Fusion / Q000502:physiology*; D009975:Orthomyxoviridae / Q000502:physiology*; D018108:Respirovirus / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000502:physiology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D014760:Viral Fusion Proteins