This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Beckham, J. D.
Right arrow Articles by Tyler, K. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Beckham, J. D.
Right arrow Articles by Tyler, K. L.

 Previous Article  |  Next Article 

Journal of Virology, May 2009, p. 5035-5045, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02433-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Reovirus Activates Transforming Growth Factor β and Bone Morphogenetic Protein Signaling Pathways in the Central Nervous System That Contribute to Neuronal Survival following Infection{triangledown}

J. David Beckham,1,4 Kathryn Tuttle,2 and Kenneth L. Tyler1,2,3,4*

Departments of Medicine,1 Neurology,2 Microbiology, University of Colorado Denver, Denver, Colorado 80045,3 Denver Veteran Affairs Medical Center, Denver, Colorado 802204

Received 25 November 2008/ Accepted 26 February 2009

Viral infections of the central nervous system (CNS) are important causes of worldwide morbidity and mortality, and understanding how viruses perturb host cell signaling pathways will facilitate identification of novel antiviral therapies. We now show that reovirus infection activates transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling in a murine model of encephalitis in vivo. TGF-β receptor I (TGF-βRI) expression is increased and its downstream signaling factor, SMAD3, is activated in the brains of reovirus-infected mice. TGF-β signaling is neuroprotective, as inhibition with a TGF-βRI inhibitor increases death of infected neurons. Similarly, BMP receptor I expression is increased and its downstream signaling factor, SMAD1, is activated in reovirus-infected neurons in the brains of infected mice in vivo. Activated SMAD1 and SMAD3 were both detected in regions of brain infected by reovirus, but activated SMAD1 was found predominantly in uninfected neurons in close proximity to infected neurons. Treatment of reovirus-infected primary mouse cortical neurons with a BMP agonist reduced apoptosis. These data provide the first evidence for the activation of TGF-β and BMP signaling pathways following neurotropic viral infection and suggest that these signaling pathways normally function as part of the host's protective innate immune response against CNS viral infection.

* Corresponding author. Mailing address: University of Colorado Denver, Dept. Neurology (B182), 12700 E. 19th Avenue, Research Complex 2-5th Floor, Aurora, CO 80045. Phone: (303) 393-2874. Fax: (303) 393-4686. E-mail: Ken.Tyler{at}uchsc.edu

{triangledown} Published ahead of print on 11 March 2009.

Journal of Virology, May 2009, p. 5035-5045, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02433-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»