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| Subject Categories: Microbiology & Pathogens |
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| The EMBO Journal
(2007) 26, 4016–4028, doi:10.1038/sj.emboj.7601831 Published online 23 August 2007 |
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| Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2 |
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| Carolyn B Coyne1, Kwang S Kim2 and Jeffrey M Bergelson1, 3 |
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1 Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA 2 Department of Pediatrics, Division of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Departments of Pediatrics and Microbiology, University of Pennsylvania, Philadelphia, PA, USA To whom correspondence should be addressed Carolyn B Coyne, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, S313 Biomedical Science Tower-South, 3500 Terrace Street, Pittsburgh, PA 15216, USA. Tel.: +1 412 383 5149; Fax: +1 412 383 6517; E-mail: coynec2@pitt.edu Received 3 April 2007; Accepted 23 July 2007; Published online 23 August 2007. |
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| Abstract |
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| 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. |
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| Keywords: blood–brain barrier, caveolin, poliovirus, SHP-2, tyrosine phosphatase |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHPoliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2 The EMBO Journal Article |
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