A picornaviral protein synthesized out of frame with the polyprotein plays a key role in a virus-induced immune-mediated demyelinating disease.
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.
Chen
H H
HH
Department of Neurology/MC2030, University of Chicago Medical Center, Illinois 60637, USA.
Kong
W P
WP
Zhang
L
L
Ward
P L
PL
Roos
R P
RP
D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D001483:Base Sequence; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis; D016366:Open Reading Frames; D011051:Poliomyelitis / Q000150:complications* / Q000276:immunology; D011498:Protein Precursors / Q000235:genetics*; D013116:Spinal Cord / Q000473:pathology; D017945:Theilovirus / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D014764:Viral Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology*
C096897:L(asterisk) protein, Theiler's encephalomyelitis virus; D008565:Membrane Proteins; D011498:Protein Precursors; D014764:Viral Proteins