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.
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-
/
) 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-
4 and IFN-
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.
This article has been cited by other articles:
| J. Bacteriol. | Mol. Cell. Biol. | Microbiol. Mol. Biol. Rev. |
|---|
| Clin. Vaccine Immunol. | ALL ASM JOURNALS |
|---|