title: Role of mutations G-480 and C-6203 in the attenuation phenotype of Sabin type 1 poliovirus.
abstract: Of the 55 point mutations which distinguish the type 1 poliovirus vaccine strain (Sabin 1) from its neurovirulent progenitor (P1/Mahoney), two have been strongly implicated by previous studies as determinants of the attenuation phenotype. A change of an A to a G at position 480, located within the 5' noncoding region, has been suggested to be the major attenuating mutation, analogous to the mutations at positions 481 and 472 in poliovirus types 2 and 3, respectively. In addition, the change of a U to a C at position 6203, resulting in an amino acid change in the polymerase protein 3D, has also been implicated as a determinant of attenuation, albeit to a lesser extent. To assess the contributions of these mutations to attenuation and temperature sensitivity, reciprocal changes were generated at these positions in infectious cDNA clones of Sabin 1 and P1/Mahoney. Assays in tissue culture and primates indicated that the two mutations make some contribution to the temperature sensitivity of the Sabin 1 strain but that neither is a strong determinant of attenuation.
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D003596:Cytosine; D018076:DNA, Complementary; D016679:Genome, Viral; D006147:Guanine; D006801:Humans; D009690:Nucleic Acid Conformation; D010641:Phenotype; D017354:Point Mutation; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014498:Uracil; D014613:Vaccines, Attenuated; D014774:Virulence / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014498:Uracil; D006147:Guanine; D003596:Cytosine