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

Content Provider	PubMed Central
Author	Coyne, Carolyn B. Kim, Kwang S. Bergelson, Jeffrey M.
Copyright Year	2007
Abstract	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.
Related Links	http://dx.doi.org/10.1038/sj.emboj.7601831
Ending Page	4028
Page Count	13
Starting Page	4016
File Format	PDF
ISSN	02614189
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	17
Volume Number	26
Language	English
Publisher	Nature Publishing Group
Publisher Date	2007-09-05
Access Restriction	Open
Rights Holder	Nature Publishing Group
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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