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Journal of Virology, January 2004, p. 250-256, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.250-256.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

A JC Virus-Induced Signal Is Required for Infection of Glial Cells by a Clathrin- and eps15-Dependent Pathway

W. Querbes,1 A. Benmerah,2 D. Tosoni,3 P. P. Di Fiore,3,4 and Walter J. Atwood1,5*

Graduate Program in Pathobiology,1 Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912,5 Department of Cell Biology, Institut Cochin, 75679 Paris, Cedex 14, France,2 Department of Experimental Oncology, European Institute of Oncology,3 IFOM, FIRC Institute for Molecular Oncology and University of Milan Medical School, 20141 Milan, Italy4

Received 9 July 2003/ Accepted 22 September 2003

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.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Brown University, Box G-B616, 171 Meeting St., Providence, RI 02912. Phone: (401) 863-3116. Fax: (401) 863-1971. E-mail: Walter_Atwood{at}Brown.edu.

Journal of Virology, January 2004, p. 250-256, Vol. 78, No. 1
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.1.250-256.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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