USE OF TYPE-1 TYPE-2 CHIMERIC POLIOVIRUSES TO STUDY DETERMINANTS OF POLIOVIRUS TYPE-1 NEUROVIRULENCE IN A MOUSE MODEL

We previously described the characteristics of a type 1 /type 2 (PV-1 / PV-2) chimeric poliovirus, v510, which contains the six amino acids specific for PV-2 in the B-C loop of VP1. This virus was found to be mouse-adapted, as PV-2 and in contrast with PV-1. Determinants of host range were studied in detail and are reported here. PV-1 /PV-2 chimeras containing partial PV-1 → PV-2 substitutions in the B-C loop of VP1 were obtained by making use of a mutagenesis cartridge on PV-1 cDNA. Analysis of mouse neurovirulence of these chimeras, when correlated with the three-dimensional structure of the v510 capsid, revealed that PV-2 residues important for mouse tropism are those which determine the particular conformation of the B-C loop of VP1 in v510. The mutation of the adenine residue at position 480 of the 5′ noncoding region into a guanine residue has been shown to be an important determinant of PV-1 attenuation in monkeys. We show that introduction of this mutation in the v510 genome results in a virus which is partially attenuated for mice. This suggests that analysis of genomic determinants important for PV-1 neurovirulence could be carried out in a mouse model by making use of a mouse-adapted PV-1/PV-2 chimera. © 1991.