The best experimental evidence indicating that viruses have an etiological role in the pathogenesis of diabetes comes from studies of mice infected with EMC virus. For this study we generated mutant viruses from stocks of diabetogenic EMC-D and nondiabetogenic EMC-B viruses by serial passages of the viruses in L-cell cultures at high MOI. The genomic sequence information and the biological activities of three different plaque-purified diabetogenic variants of EMC virus (EMC-D, EMC-D1/6A, EMC-D2/4) and six different plaque-purified nondiabetogenic variants (EMC-B, EMC-BS, EMC-B1/G, EMC-DV1, EMC-D4/1B, EMC-D3/1) revealed that only one amino acid, Ala (776th amino acid on the polyprotein), is critical for the diabetogenicity of EMC virus. The G base at the nucleotide position 3155 (Ala[GCC]776 in the polyprotein) is unique to all diabetogenic variants, whereas the A base at the same position (Thr[ACC]776 in the polyprotein) is identical to all nondiabetogenic variants. A single-point mutation (G to A; Ala to Thr) results in the conversion of the diabetogenic variant into a nondiabetogenic variant of EMC virus. On the basis of these observations, we conclude that a single amino acid, Ala776, on the polyprotein of EMC virus appears responsible for the inducement of diabetes in susceptible mice. Conversion of Ala776 into Thr776 on the polyprotein by a point mutation, G to A at the nucleotide position 3155, results in the loss of diabetogenicity.
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Original Articles|
March 01 1993
Determination of Diabetogenicity Attributable to a Single Amino Acid, Ala776, on the Polyprotein of Encephalomyocarditis Virus
Yong-Soo Bae;
Yong-Soo Bae
Julia McFarlane Diabetes Research Centre and the Department of Microbiology and Infectious Diseases, University of Calgary
Calgary, Alberta, Canada
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Ji-Won Yoon
Ji-Won Yoon
Julia McFarlane Diabetes Research Centre and the Department of Microbiology and Infectious Diseases, University of Calgary
Calgary, Alberta, Canada
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Address correspondence and reprint requests to Dr. Ji-Won Yoon, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, The University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Diabetes 1993;42(3):435–443
Article history
Received:
April 11 1992
Revision Received:
October 22 1992
Accepted:
October 22 1992
Citation
Yong-Soo Bae, Ji-Won Yoon; Determination of Diabetogenicity Attributable to a Single Amino Acid, Ala776, on the Polyprotein of Encephalomyocarditis Virus. Diabetes 1 March 1993; 42 (3): 435–443. https://doi.org/10.2337/diab.42.3.435
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