CHARACTERIZATION OF AN ANTIGENIC SITE ON THE RABIES VIRUS GLYCOPROTEIN MOLECULE (EPITOPE, DETERMINANT)

CAROLYN LESLIE SMITH, University of Pennsylvania

Abstract

The antigenic structure of the rabies virus glycoprotein has been studied in detail because it is the only rabies virus antigen which induces and binds virus-neutralizing antibodies. Antigenic sites on the glycoproteins of two tissue culture-adapted (fixed) rabies virus strains (ERA and CVS-11) were previously defined on an operational basis. The localization and structural characterization of one antigenic site (site III) which was common to both strains was of particular interest because this site had the largest representation of epitopes within any of the operationally defined sites and included an epitope which was linked with the pathogenicity of the virus. Antigenic site III was defined within the glycoprotein molecule by determining the nucleotide sequences of the glycoprotein genes of antigenic variants of ERA and CVS-11 viruses and comparing the deduced amino acid sequences to that of the parent viruses. Single amino acid substitutions were thereby identified in the glycoprotein of each variant virus which altered an epitope (antibody-binding site) assumed to be on the glycoprotein surface. The residues at positions 333 of ERA and CVS-11, 336 of ERA, 338 of CVS-11, and 357 of ERA parent virus glycoproteins were associated with site III epitopes. Local conformational alterations due to certain single amino acid substitutions in the glycoproteins at the above positions were predicted by a computer analysis of protein secondary structure (E. Golub). Biochemical data supporting prediction of local conformational change was drawn from another CVS-11 variant virus glycoprotein (associated with site II). A model of the physical association of epitopes of antigenic site III is described which considers molecular conformation. The model suggests that presence of three structurally-overlapping epitopes and one structurally-nonoverlapping epitope which correlate with the functional relationships indicated by the operational epitope map. A comparison of deduced glycoprotein sequences from three fixed rabies viruses (ERA, CVS-11, and Kelev) suggested the additional involvement of residues at positions 339, 346, and 370 in site III epitopes. The deduced glycoprotein sequences of these viruses, together with attenuated Flury HEP virus and neuroblastoma cell-selected virulent Flury HEP virus, were also compared to show more extensively that viral pathogenicity is dependent upon the presence of arginine at glycoprotein residue 333.

Subject Area

Microbiology

Recommended Citation

SMITH, CAROLYN LESLIE, "CHARACTERIZATION OF AN ANTIGENIC SITE ON THE RABIES VIRUS GLYCOPROTEIN MOLECULE (EPITOPE, DETERMINANT)" (1986). Dissertations available from ProQuest. AAI8614875.
https://repository.upenn.edu/dissertations/AAI8614875

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