GAIN OR LOSS OF DIABETOGENICITY RESULTING FROM A SINGLE-POINT MUTATION IN RECOMBINANT ENCEPHALOMYOCARDITIS VIRUS

Molecular pathogenic mechanisms for virus-induced disease have receive d considerable attention. Encephalomyocarditis (EMC) virus-induced dia betes in mice has been extensively studied to elucidate the cellular a nd molecular mechanisms involved in the development of this disease. I n this study, we report for the first time that a single point mutatio n at nucleotide position 3155 or 3156 of the recombinant EMC viral gen ome, located on the major capsid protein VP1, which causes an amino ac id change, results in the gain or loss of viral diabetogenicity. A G b ase at nucleotide position 3155 (alanine at amino acid position 776 of the EMC virus polyprotein [Ala(776)]; <(G)under bar CC>) results in v iral diabetogenicity, whereas the substitution of other bases at the s ame or next position results in a loss of viral diabetogenicity. This finding provides clear evidence that a point mutation at a critical si te in a viral genome affects the ability of the virus to cause a cell- specific disease.