A JC virus-induced signal is required for infection of glial cells by a clathrin- and eps15-dependent pathway.
Infectious entry of JC virus (JCV) into human glial cells occurs by receptor-mediated clathrin-dependent endocytosis. In this report we demonstrate that the tyrosine kinase inhibitor genistein blocks virus entry and inhibits infection. Transient expression of dominant-negative eps15 mutants, including a phosphorylation-defective mutant, inhibited both virus entry and infection. We also show that the JCV-induced signal activates the mitogen-activated protein kinases ERK1 and ERK2. These data demonstrate that JC virus binding to human glial cells induces an intracellular signal that is critical for entry and infection by a ligand-inducible clathrin-dependent mechanism.
Querbes
W
W
Graduate Program in Pathobiology, Brown University, Providence, Rhode Island 02912, USA.
Benmerah
A
A
Tosoni
D
D
Di Fiore
P P
PP
Atwood
Walter J
WJ
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones / Q000494:pharmacology; D007577:JC Virus / Q000472:pathogenicity*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009457:Neuroglia / Q000821:virology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002966:Clathrin; C486206:EPS15 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D007529:Isoflavones; D010750:Phosphoproteins; C040641:genistin; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases