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Journal of Virology, July 2003, p. 7903-7913, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7903-7913.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Sendai Virus Targets Inflammatory Responses, as Well as the Interferon-Induced Antiviral State, in a Multifaceted Manner

Laura Strähle,1 Dominique Garcin,1 Philippe Le Mercier,1 Joerg F. Schlaak,2,{dagger} and Daniel Kolakofsky1*

Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, CH1211 Geneva, Switzerland,1 Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom2

Received 13 February 2003/ Accepted 17 April 2003

We have used cDNA arrays to compare the activation of various cellular genes in response to infection with Sendai viruses (SeV) that contain specific mutations. Three groups of cellular genes activated by mutant SeV infection, but not by wild-type SeV, were identified in this way. While some of these genes are well known interferon (IFN)-stimulated genes, others, such as those for interleukin-6 (IL-6) and IL-8, are not directly induced by IFN. The gene for beta IFN (IFN-ß), which is critical for initiating an antiviral response, was also specifically activated in mutant SeV infections. The SeV-induced activation of IFN-ß was found to depend on IFN regulatory factor 3, and the activation of all three cellular genes was independent of IFN signaling. Mutations that disrupt four distinct elements in the SeV genome (the leader RNA, two regions of the C protein, and the V protein) all lead to enhanced levels of IFN-ß mRNA, and at least three of these viral genes also appear to be involved in preventing activation of IL-8. Our results suggest that SeV targets the inflammatory and adaptive immune responses as well as the IFN-induced intracellular antiviral state by using a multifaceted approach.


* Corresponding author. Mailing address: Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, 9 Ave de Champel, CH1211 Geneva, Switzerland. Phone: 41 22 379 5657. Fax: 41 22 379 5702. E-mail: Daniel.Kolakofsky{at}medecine.unige.ch.

{dagger} Present address: Department of Gastroenterology and Hepatology, University of Essen, 45122 Essen, Germany.


Journal of Virology, July 2003, p. 7903-7913, Vol. 77, No. 14
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.14.7903-7913.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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