A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus–ind

Abstract

The DA strain and other members of the TO subgroup of Theiler's murine encephalomyelitis virus (TMEV) induce a chronic demyelinating disease with a restricted virus expression. This disease serves as an experimental model of multiple sclerosis; in both diseases the immune system contributes to a similar demyelinating pathology. Like all picornaviruses, TMEV encodes a polyprotein translated from one long open reading frame. The polyprotein is then processed into structural and non–structural viral proteins. Here, we demonstrate that the DA strain of TMEV has an additional alternative open reading frame that encodes a protein called L* that is present in infected cells. Virus with a mutation of L* has a dramatically decreased demyelinating activity, indicating that L* plays a critical role in TO subgroup–induced demyelinating disease. L* is associated with membranes, suggesting that L* may interact with the immune system and thereby mediate the viral–induced demyelinating disease.

Cite this article

Chen, HH., Kong, WP., Zhang, L. et al. A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus–induced immune–mediated demyelinating disease. Nat Med 1, 927–931 (1995). https://doi.org/10.1038/nm0995-927

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