TRANSGENIC MICE CARRYING THE HUMAN POLIOVIRUS RECEPTOR - NEW ANIMAL-MODEL FOR STUDY OF POLIOVIRUS NEUROVIRULENCE

Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histo pathological lesions, and viral antigens as parameters of neurovirulen ce of the viruses. These parameters observed in the Tg mice were diffe rent for different inoculated viruses. Dose-dependent incidences of pa ralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirul ence of individual viruses estimated by the Tg mouse model had a stron g correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome o f poliovirus that had been identified by monkey tests. In addition, th e mouse tests revealed new neurovirulence determinants, that is, diffe rent nucleotides between the two strains at positions 189 and 21 and/o r 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this s tudy may be suitable for replacing monkeys for investigating polioviru s neurovirulence.