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 resistanc e to tumor cells by acting as a transporter that blocks: the entry into the cell of a great variety of drugs and hydrophobic pep tides. 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 th at the fusion of the viral envelope with the plasma membrane of these cells is impaired. Multidrug-resistant cells display significant resistance to i nfection by envelope viruses that invade cells by fusion with the plasma me mbrane, but not to infection by pH-dependent viruses that penetrate cells b y 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.