The leader protein of Theiler's virus inhibits immediate-early alpha/beta interferon production.
(2001) Journal of Virology — Vol. 75, n° 17, p. 7811-7817 (2001)
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- 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-alpha4 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.
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Van Pesch, V., van Eyll, O., & Michiels, T. (2001). The leader protein of Theiler’s virus inhibits immediate-early alpha/beta interferon production. Journal of Virology, 75(17), 7811-7817. https://doi.org/10.1128/JVI.75.17.7811-7817.2001 (Original work published 2001)