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P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane¹

Intramural Research Support Program SAIC Frederick, Laboratory of Experimental and Computational Biology and
^* Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick Maryland 21702, USA

²Correspondence: Intramural Research Support Program SAIC Frederick, Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research and Development Center, Bldg. 469, Room 211, NCI-FCRDC, Frederick MD 21702, USA. E-mail: yraviv{at}mail.ncifcrf.gov

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., Puri, A., Blumenthal, R. P-glycoprotein-overexpressing multidrug-resistant cells are resistant to infection by enveloped viruses that enter via the plasma membrane.

Key Words: viral invasion • membrane fusion • photosensitized labeling • hydrophobic labeling

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