Canyon rim residues, including antigenic determinants, modulate serotype-specific binding of polioviruses to mutants of the poliovirus receptor

Abstract

Several mouse cell lines expressing hybrid human poliovirus receptors (hPVRs) bearing mutations in the first immunoglobulin-like domain were previously characterized for their defective binding and replication of poliovirus type 1 Mahoney (G. Bernhardt, J. Harber, A. Zibert, M. DeCrombrugghe, and E. Wimmer, Virology, 203, 344-356, 1994). Here we report that these mutant hPVRs were utilized to explore differences in the binding behavior of the three serotypes of poliovirus. Type 3 polioviruses (both Sabin and the neurovirulent Leon strain) clearly bound to the hPVR mutant Q130G/GD, but were incapable of initiating infection. Also, binding at 25° of poliovirus types 2 and 3 to cell lines expressing the hPVR mutants P84SYS/HPGA, L99GAE/AAAA, and D117F was greater than type 1 poliovirus. Further study of the serotype-specific interaction with mutant hPVRs was accomplished with antigenic hybrid viruses. Improved binding by antigenic hybrid viruses demonstrated that serotype-specific binding to mutant hPVRs is, in part, determined by the amino acid sequence of neutralization antigenic sites (NAgs) and the probable conformational rearrangement of amino acids adjacent to the NAg sites. Finally, site-directed mutants of poliovirus were utilized to determine the relative contributions, to hPVR interactions, of individual amino acids with solvent accessible side chains in the viral canyon. Of the 18 viable virus mutants produced, 3 (D1226A, I1089A, and VPEK1166HPGA) expressed impaired replication phenotypes on the mutant hPVR cell lines P84SYS/ HYSA and D117F. A location at the rim of the poliovirus canyon was implicated for the interaction of the amino terminal domain of the poliovirus receptor with conserved and serotype-specific viral surface amino acids. The possible involvement of elements of neutralization antigenic sites in receptor binding may explain, in part, why poliovirus exists in only three serotypes. © 1995 Academic Press, Inc.