Integrin-mediated signaling induced by simian virus 40 leads to transient uncoupling of cortical actin and the plasma membrane

PLoS One. 2013;8(2):e55799. doi: 10.1371/journal.pone.0055799. Epub 2013 Feb 7.

Abstract

Simian Virus 40 (SV40) is a paradigm pathogen with multivalent binding sites for the sphingolipid GM1, via which it induces its endocytosis for infection. Here we report that SV40 also utilizes cell surface integrins to activate signaling networks required for infection, even in the absence of the previously implicated glycosphingolipids. We identify ILK, PDK1, the RhoGAP GRAF1 and RhoA as core nodes of the signaling network activated upon SV40 engagement of integrins. We show that integrin-mediated signaling through host SV40 engagement induces the de-phosphorylation of Ezrin leading to uncoupling of the plasma membrane and cortical actin. Our results provide functional evidence for a mechanism by which SV40 activates signal transduction in human epithelial cells via integrins in the context of clathrin-independent endocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Cell Adhesion / physiology
  • Cell Line
  • Cell Membrane / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Epistasis, Genetic
  • Gene Regulatory Networks
  • Glycosphingolipids / metabolism
  • Humans
  • Integrins / metabolism*
  • Membrane Glycoproteins / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Polyomavirus Infections / genetics
  • Polyomavirus Infections / metabolism
  • Protein Binding
  • Protein Interaction Maps
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteomics
  • Proto-Oncogene Proteins c-akt
  • Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase
  • RNA Interference
  • Signal Transduction*
  • Simian virus 40 / physiology*
  • Virus Internalization
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Actins
  • Cytoskeletal Proteins
  • Glycosphingolipids
  • Integrins
  • Membrane Glycoproteins
  • PDK1 protein, human
  • Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase
  • ezrin
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • rhoA GTP-Binding Protein

Grant support

This work was supported by the Bonizzi-Theler Foundation (LS), the Swiss National Science Foundation (LP), the National Center of Competence in Research (NCCR) Neural Plasticity and Repair (BW), and the InfectX project within the Swiss Initiative in Systems Biology (BW, LP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.