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Journal of Virology, September 2001, p. 7811-7817, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.7811-7817.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

The Leader Protein of Theiler's Virus Inhibits Immediate-Early Alpha/Beta Interferon Production

Vincent van Pesch, Olivier van Eyll, and Thomas Michiels*

Christian de Duve Institute of Cellular Pathology, University of Louvain, B-1200 Brussels, Belgium

Received 2 February 2001/Accepted 31 May 2001

Theiler's virus is a picornavirus responsible for a persistent infection of the central nervous system of the mouse, leading to a chronic demyelinating disease considered to be a model for multiple sclerosis. The leader (L) protein encoded by Theiler's virus is a 76-amino-acid-long peptide containing a zinc-binding motif. This motif is conserved in the L proteins of all cardioviruses, including encephalomyocarditis virus. The L protein of Theiler's virus was suggested to interfere with the alpha/beta interferon (IFN-alpha /beta ) response (W.-P. Kong, G. D. Ghadge, and R. P. Roos, Proc. Natl. Acad. Sci. USA 91:1796-1800, 1994). We show that expression of the L protein indeed inhibits the production of alpha/beta interferon by infected L929 cells. The L protein specifically inhibits the transcription of the IFN-alpha 4 and IFN-beta genes, which are known to be activated early in response to viral infection. Mutation of the zinc finger was sufficient to block the anti-interferon activity, outlining the importance of this motif in the L protein function. In agreement with the anti-interferon role of the L protein, a virus bearing a mutation in the zinc-binding motif was dramatically impaired in its ability to persist in the central nervous system of SJL/J mice.

* Corresponding author. Mailing address: Christian de Duve Institute of Cellular Pathology, University of Louvain, MIPA-VIRO 74-49, 74, avenue Hippocrate, B-1200 Brussels, Belgium. Phone: 32 2 764 74 29. Fax: 32 2 764 74 95. E-mail: michiels{at}mipa.ucl.ac.be.

Journal of Virology, September 2001, p. 7811-7817, Vol. 75, No. 17
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.17.7811-7817.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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