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Journal of Virology, August 2001, p. 6800-6807, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.6800-6807.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Longer and Shorter Forms of Sendai Virus C Proteins Play Different Roles in Modulating the Cellular Antiviral Response

Dominique Garcin,1 Joseph Curran,1 Masae Itoh,2 and Daniel Kolakofsky1,*

Department of Genetics and Microbiology, University of Geneva School of Medicine, CH1211 Geneva, Switzerland,1 and Osaka Prefectural Institute of Public Health, Higashinari, 537-0025 Osaka, Japan2

Received 25 January 2001/Accepted 25 April 2001

The Sendai virus (SeV) C gene codes for a nested set of four C proteins that carry out several functions, including the modulation of viral RNA synthesis and countering of the cellular antiviral response. Using mutant C genes (and in particular a C gene with a deletion of six amino acids present only in the larger pair of C proteins) and recombinant SeV carrying these mutant C genes, we find that the nested set of C proteins carry out a nested set of functions. All of the C proteins interdict interferon (IFN) signaling to IFN-stimulated genes (ISGs) and prevent pY701-Stat1 formation. However, only the larger C proteins can induce STAT1 instability, prevent IFN from inducing an antiviral state, or prevent programmed cell death. Remarkably, interdiction of IFN signaling to ISGs and the absence of pY701-Stat1 formation did not prevent IFN-alpha from inducing an anti-Vesicular stomatitis virus (VSV) state. It is possible that IFN-alpha signaling to induce an anti-VSV state can occur independently of the well-established Jak/Stat/ISGF3 pathway and that it is this parallel pathway that is targeted by the longer C proteins.


* Corresponding author. Mailing address: Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, 9 Ave. de Champel, CH1211 Geneva, Switzerland. Phone: 41-22-702-56-57. Fax: 41-22-702-57-02. E-mail: Daniel.Kolakofsky{at}Medecine.unige.ch.


Journal of Virology, August 2001, p. 6800-6807, Vol. 75, No. 15
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.15.6800-6807.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.



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