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

Author:

Querbes W.1,Benmerah A.2,Tosoni D.3,Di Fiore P. P.34,Atwood Walter J.15

Affiliation:

1. Graduate Program in Pathobiology

2. Department of Cell Biology, Institut Cochin, 75679 Paris, Cedex 14, France

3. Department of Experimental Oncology, European Institute of Oncology

4. IFOM, FIRC Institute for Molecular Oncology and University of Milan Medical School, 20141 Milan, Italy

5. Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

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