Two amino acids, Phe 16 and Ala 776, on the polyprotein are most likely to be responsible for the diabetogenicity of encephalomyocarditis virus.
The diabetogenic D variant of encephalomyocarditis virus (EMC-D) was previously shown to differ from the non-diabetogenic B variant (EMC-B) by 14 nucleotides out of 7829 bases. Similar approaches with a new nondiabetogenic variant, EMC-DV1, obtained by plaque purification of the EMC-D variant stock pool, enabled us to narrow down further the possible genomic area responsible for the diabetogenicity of EMC virus. EMC-DV1 does not induce interferon in vitro, differing from the highly interferon-inducing EMC-B. The complete nucleotide sequence of EMC-DV1 was determined by RNA-dependent DNA sequencing and cDNA sequencing. The genomic size and organization of EMC-DV1 are similar to those of EMC-D and EMC-B, with a long open reading frame encoding a polyprotein of 2292 amino acids. Comparative analyses of sequence information as well as biological activities of EMC-DV1 with EMC-D and EMC-B suggest that (i) the diabetogenicity is apparently distinct from the ability to induce interferon, which is probably due to the single U base insertion at position 765 in EMC-B, and (ii) the diabetogenicity of EMC virus is most probably controlled by one or both of two amino acids, Phe 16 (on the leader peptide) and Ala 776 (152nd amino acid on the VP1) on the polyprotein.
Department of Microbiology and Infectious Diseases, Julia McFarlane Diabetes Research Centre, University of Calgary, Alberta, Canada.
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D000409:Alanine; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000382:microbiology*; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000472:pathogenicity*; D005814:Genes, Viral; D014644:Genetic Variation; D007372:Interferons / Q000096:biosynthesis; D007739:L Cells / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010649:Phenylalanine; D015183:Restriction Mapping; D014764:Viral Proteins / Q000235:genetics*
D003062:Codon; D004279:DNA, Viral; D014764:Viral Proteins; D010649:Phenylalanine; D007372:Interferons; D000409:Alanine