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Enterovirus 71 triggering of neuronal apoptosis through activation of Abl‐Cdk5 signalling

Enterovirus 71 triggering of neuronal apoptosis through activation of Abl‐Cdk5 signalling Summary The molecular mechanism behind what causes an infection of Enterovirus 71 (EV71) in young children to result in severe neurological diseases is unclear. Herein, we show that Cdk5, a critical signalling effector of various neurotoxic insults in the brain, is activated by EV71 infection of neuronal cells. EV71‐induced neuronal apoptosis could be effectively repressed by blocking either Cdk5 kinase activity or its protein expression. Moreover, EV71‐induced Cdk5 activation was modulated by c‐Abl. The suppression of c‐Abl kinase activity by STI571 notably repressed both the Cdk5 activation and neuronal apoptosis in cells infected with EV71. Although EV71 also induces apoptosis in non‐neuronal cells, it did not affect Abl and Cdk5 activities in several non‐neuronal cell lines. Intriguingly, coxsackievirus A16 (CA16), a genetically closely related serotype to EV71 that usually does not induce severe neurological disorders, could only weakly stimulate Abl, but not Cdk5 kinase activity. Taken together, our data suggest a serotype‐ and cell type‐specific mechanism, by which EV71 induces Abl kinase activity, which in turn triggers Cdk5‐signalling for neuronal apoptosis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cellular Microbiology Wiley

Enterovirus 71 triggering of neuronal apoptosis through activation of Abl‐Cdk5 signalling

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References (51)

Publisher
Wiley
Copyright
Copyright © 2007 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1462-5814
eISSN
1462-5822
DOI
10.1111/j.1462-5822.2007.00988.x
pmid
17581253
Publisher site
See Article on Publisher Site

Abstract

Summary The molecular mechanism behind what causes an infection of Enterovirus 71 (EV71) in young children to result in severe neurological diseases is unclear. Herein, we show that Cdk5, a critical signalling effector of various neurotoxic insults in the brain, is activated by EV71 infection of neuronal cells. EV71‐induced neuronal apoptosis could be effectively repressed by blocking either Cdk5 kinase activity or its protein expression. Moreover, EV71‐induced Cdk5 activation was modulated by c‐Abl. The suppression of c‐Abl kinase activity by STI571 notably repressed both the Cdk5 activation and neuronal apoptosis in cells infected with EV71. Although EV71 also induces apoptosis in non‐neuronal cells, it did not affect Abl and Cdk5 activities in several non‐neuronal cell lines. Intriguingly, coxsackievirus A16 (CA16), a genetically closely related serotype to EV71 that usually does not induce severe neurological disorders, could only weakly stimulate Abl, but not Cdk5 kinase activity. Taken together, our data suggest a serotype‐ and cell type‐specific mechanism, by which EV71 induces Abl kinase activity, which in turn triggers Cdk5‐signalling for neuronal apoptosis.

Journal

Cellular Microbiology – Wiley

Published: Nov 1, 2007

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