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A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus–induced immune–mediated demyelinating disease

Nature Medicine volume 1, pages 927–931 (1995)Cite this article

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.

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Authors and Affiliations

  1. Department of Neurology/MC2030, University of Chicago Medical Center, Chicago, Illinois, 60637, USA

    Hsiao-Huei Chen, Liang Zhang & Raymond P. Roos

  2. Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, 48109, USA

    Wing-Pui Kong

  3. Marjorie B. Kovler Viral Oncology Laboratories, University of Chicago, Chicago, Illinois, 60637, USA

    Patricia L. Ward

Authors
  1. Hsiao-Huei Chen
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  2. Wing-Pui Kong
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  4. Patricia L. Ward
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  5. Raymond P. Roos
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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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