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Journal of Virology, August 1999, p. 6559-6565, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Sendai Virus C Proteins Counteract the Interferon-Mediated Induction of an Antiviral State

Dominique Garcin, Patrizia Latorre, and Daniel Kolakofsky*

Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, CH1211 Geneva, Switzerland

Received 16 March 1999/Accepted 5 May 1999

We have studied the relationship between the Sendai virus (SeV) C proteins (a nested set of four proteins initiated at different start codons) and the interferon (IFN)-mediated antiviral response in IFN-competent cells in culture. SeV strains containing wild-type or various mutant C proteins were examined for their ability (i) to induce an antiviral state (i.e., to prevent the growth of vesicular stomatitis virus [VSV] following a period of SeV infection), (ii) to induce the elevation of Stat1 protein levels, and (iii) to prevent IFN added concomitant with the SeV infection from inducing an antiviral state. We find that expression of the wild-type C gene and, specifically, the AUG114-initiated C protein prevents the establishment of an antiviral state: i.e., cells infected with wild-type SeV exhibited little or no increase in Stat1 levels and were permissive for VSV replication, even in the presence of exogenous IFN. In contrast, in cells infected with SeV lacking the AUG114-initiated C protein or containing a single amino acid substitution in the C protein, the level of Stat1 increased and VSV replication was inhibited. The prevention of the cellular IFN-mediated antiviral response appears to be a key determinant of SeV pathogenicity.

* Corresponding author. Mailing address: Department of Genetics and Microbiology, University of Geneva School of Medicine, CMU, 9 Ave. de Champel, CH1211 Geneva, Switzerland. Phone: (4122) 702 5657. Fax: (41 22) 702 5702. E-mail: Daniel.Kolakofsky{at}Medecine.unige.ch.

Journal of Virology, August 1999, p. 6559-6565, Vol. 73, No. 8
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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