Sequence homology between encephalomyocarditis virus protein VPI and histidyl-tRNA synthetase supports a hypothesis of molecular mimicry in polymyositis.
The amino acid sequence of histidyl-tRNA synthetase, the Jo-I antigen of polymyositis, has been compared with that of the polyprotein of encephalomyocarditis virus (EMCV), an agent shown recently to produce polymyositis symptoms in mice. It is shown that there is significant sequence homology between a region of the synthetase formerly identified by us as a possible epitope and a region on the coat protein VPI of EMCV. The viral protein also shows significant sequence homology with several muscle proteins. Identification of the likely spatial location of the VPI sequence on the shell of the virus by comparison with two other picornaviruses whose three dimensional structures have been determined, reveals it to be homologous with known immunogenic sites on these viruses. Independent structural localisation of the possible epitope by comparison with two aminoacyl-tRNA synthetases, whose three dimensional structures are known, also reveals that the sequence in question is likely to be favourably placed on histidyl-tRNA synthetase to crossreact with appropriate antibodies. These findings provide more definitive evidence in support of our previous suggestion that molecular mimicry could explain the origin of serum antibodies to aminoacyl-tRNA synthetases in polymyositis and suggests a likely viral etiology for the disease.
Walker
E J
EJ
Protein Chemistry Group, John Curtin School of Medical Research, Australian National University, Canberra, A.C.T.
Jeffrey
P D
PD
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D002213:Capsid / Q000201:enzymology / Q000276:immunology; D004686:Encephalomyocarditis virus / Q000201:enzymology / Q000276:immunology*; D006643:Histidine-tRNA Ligase / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009220:Myositis / Q000201:enzymology / Q000276:immunology*; D012689:Sequence Homology, Nucleic Acid
D000914:Antibodies, Viral; D000604:Amino Acyl-tRNA Synthetases; D006643:Histidine-tRNA Ligase