Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2.

Journal Article (Journal Article)

Viruses use specific receptor molecules to bind selectively to target cells. Receptors have often been considered as mere docking sites, but they may also possess intrinsic signaling capacities that serve to prime the cell for entry and infection. Poliovirus (PV) initiates infection by binding to the PV receptor (PVR) and causes paralytic poliomyelitis by replicating within motor neurons of the brain and spinal cord. We have examined the process by which PV enters cultured human brain microvascular endothelial cells (HBMEC), an in vitro model of the blood-brain barrier. We found that PV enters HBMEC by dynamin-dependent caveolar endocytosis, and that entry depends on intracellular signals triggered by virus attachment to PVR. Tyrosine kinase and RhoA GTPase activation initiated by PVR ligation were both essential. Virus attachment also induced tyrosine phosphorylation of PVR; this permitted the association of PVR with SHP-2, a protein tyrosine phosphatase whose activation was required for entry and infection. The results indicate that receptor-induced signals promote virus entry and suggest a role for tyrosine phosphatases in viral pathogenesis.

Full Text

Duke Authors

Cited Authors

  • Coyne, CB; Kim, KS; Bergelson, JM

Published Date

  • September 5, 2007

Published In

Volume / Issue

  • 26 / 17

Start / End Page

  • 4016 - 4028

PubMed ID

  • 17717529

Pubmed Central ID

  • PMC1994131

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1038/sj.emboj.7601831

Language

  • eng

Conference Location

  • England