Determination of encephalomyocarditis viral diabetogenicity by a putative binding site of the viral capsid protein
Yoon, Ho Sup
Kim, Ki Hwan
Notkins, Abner L.
Date of Issue1998
School of Biological Sciences
The molecular mechanism by which some, but not all, variants of encephalomyocarditis (EMC) virus selectively infect pancreatic beta-cells in mice and induce IDDM has been an enigma for more than a decade. We report here that the binding site of the EMC viral capsid protein VP1 determines viral diabetogenicity. Recombinant chimeric EMC viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 of the major capsid protein VP1 bind poorly to beta-cells. In contrast, recombinant chimeric EMC viruses containing alanine or glycine at position 152 of the VP1 bind efficiently to and infect beta-cells, resulting in the development of diabetes. Three-dimensional molecular modeling reveals that the van der Waals interactions are greater and the residues surrounding position 152 of the VP1 are more closely packed in recombinant chimeric viruses containing threonine, serine, proline, aspartic acid, or valine at position 152 than in recombinant chimeric viruses containing alanine or glycine at the same position. Our studies reveal that the surface areas surrounding alanine or glycine at position 152 of the VP1 are more accessible, thus increasing the availability of the binding sites for attachment to beta-cell receptors and resulting in viral infection and the development of diabetes.
© 1998 American Diabetes Association. This is the author created version of a work that has been peer reviewed and accepted for publication by Diabetes, American Diabetes Association. It incorporates referee’s comments but changes resulting from the publishing process, such as copyediting, structural formatting, may not be reflected in this document. The published version is available at: http://dx.doi.org/10.2337/diabetes.47.4.576