help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on October 6, 2005, doi:10.1165/rcmb.2004-0417OC

Am. J. Respir. Cell Mol. Biol., Volume 34, Number 2, February 2006, 192-203

A more recent version of this article appeared on February 1, 2006
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
2004-0417OCv1
34/2/192    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, Y.
Right arrow Articles by Wu, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, Y.
Right arrow Articles by Wu, R.

Submitted on December 28, 2004
Revised on September 26, 2005

Rhinovirus Induces Airway Epithelial Gene Expression through dsRNA and Interferon-dependent Pathways

Yin Chen1*, Edward Hamati1, Pak-Kei Lee1, Wai-Ming Lee2, Shinichiro Wachi1, David Schnurr3, Shigeo Yagi3, Gregory Dolganov4, Homer Boushey4, Pedro Avila4, and Reen Wu1

1 Department of Internal Medicine, University of California at Davis, Davis, CA, USA, 2 Department of Pediatrics, University of Wisconsin, Madison, WI, USA, 3 California Department of Health Services, Richmond, Richmond, CA, USA, 4 Department of Medicine, University of California at San Francisco, San Francisco, CA, USA

* To whom correspondence should be addressed. E-mail: yinchen{at}ucdavis.edu.

Rhinovirus (RV) infection is the major cause of common colds and of asthma exacerbations. Because epithelial cell layer is the primary target of RV infection, we hypothesize that RV-induced airway diseases is associated with the perturbation of the airway epithelial gene expression. In this study, well-differentiated primary human airway epithelial cells were infected with either RV16 (major group) or RV1B (minor group). Transcriptional gene profiles from RV-infected and mock-infected control cells were analyzed by Affymetrix GenechipTM, and changes of the gene expression were confirmed by real-time RT-PCR analysis. Twenty-four hours after infection, 48 genes induced by both viruses were identified. Most of these genes are related to the interferon pathway and have been documented to have anti-viral functions. Indeed, a significant stimulation of IFN{beta} secretion was detected after RV16 infection. Neutralizing antibody specific to IFN{beta} and a specific inhibitor of JAK pathway both significantly blocked the induction of RV inducible genes. Further studies demonstrated that 2-aminopurine, a specific inhibitor double-stranded RNA (dsRNA)-dependent protein kinase (PKR) could block both IFN{beta} production and RV-induced gene expression. Thus, IFN{beta} dependent pathway is a part of the dsRNA-initiated pathway that is responsible for RV-induced gene expression. Consistent with its indispensable role in the induction of antiviral genes, deactivation of this signaling pathway significantly enhanced viral production. Because increase of viral yield is associated with the severity of RV-induced airway illness, the discovery of epithelial antiviral signaling pathway in this study will contribute to our understanding of the pathogenesis of RV-induced colds and asthma exacerbations.




This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
D. Proud, R. B. Turner, B. Winther, S. Wiehler, J. P. Tiesman, T. D. Reichling, K. D. Juhlin, A. W. Fulmer, B. Y. Ho, A. A. Walanski, et al.
Gene Expression Profiles during In Vivo Human Rhinovirus Infection: Insights into the Host Response
Am. J. Respir. Crit. Care Med., November 1, 2008; 178(9): 962 - 968.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
D. C. Newcomb, U. S. Sajjan, D. R. Nagarkar, Q. Wang, S. Nanua, Y. Zhou, C. L. McHenry, K. T. Hennrick, W. C. Tsai, J. K. Bentley, et al.
Human Rhinovirus 1B Exposure Induces Phosphatidylinositol 3-Kinase-dependent Airway Inflammation in Mice
Am. J. Respir. Crit. Care Med., May 15, 2008; 177(10): 1111 - 1121.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. C. Newcomb, U. S. Sajjan, D. R. Nagarkar, A. M. Goldsmith, J. K. Bentley, and M. B. Hershenson
Cooperative effects of rhinovirus and TNF-{alpha} on airway epithelial cell chemokine expression
Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L1021 - L1028.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
J. Yoo, H. Tcheurekdjian, S. V. Lynch, M. Cabana, and H. A. Boushey
Microbial Manipulation of Immune Function for Asthma Prevention: Inferences from Clinical Trials
Proceedings of the ATS, July 1, 2007; 4(3): 277 - 282.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
Z. Allakhverdi, M. R. Comeau, H. K. Jessup, B.-R. P. Yoon, A. Brewer, S. Chartier, N. Paquette, S. F. Ziegler, M. Sarfati, and G. Delespesse
Thymic stromal lymphopoietin is released by human epithelial cells in response to microbes, trauma, or inflammation and potently activates mast cells
J. Exp. Med., February 19, 2007; 204(2): 253 - 258.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. L. Korpi-Steiner, M. E. Bates, W.-M. Lee, D. J. Hall, and P. J. Bertics
Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation
J. Leukoc. Biol., December 1, 2006; 80(6): 1364 - 1374.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Proud and C.-W. Chow
Role of Viral Infections in Asthma and Chronic Obstructive Pulmonary Disease
Am. J. Respir. Cell Mol. Biol., November 1, 2006; 35(5): 513 - 518.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2005 American Thoracic Society. 		  ATS Best of the Web