title: A mutation present in the amino terminus of Sabin 3 poliovirus VP1 protein is attenuating.
abstract: The attenuated phenotype of Sabin 3 poliovirus compared with its neurovirulent progenitor strain has been largely accounted for by mutations in the genome at positions 472 and 2034 (G. D. Westrop, K. A. Wareham, D. M. A. Evans, G. Dunn, P. D. Minor, D. I. Magrath, F. Taffs, S. Marsden, M. A. Skinner, G. C. Schild, and J. W. Almond, J. Virol. 63:1338-1344, 1989). By sequencing vaccine virus RNA, we recently identified another Sabin 3-specific mutation at position 2493 (U----C), which predicts an Ile----Thr change at the sixth residue of VP1 (C. Weeks-Levy, J. M. Tatem, S. J. DiMichele, W. Waterfield, A. F. Georgiu, and S. J. Mento, Virology 185:934-937, 1991). Viruses generated by using cDNAs which represent the vaccine sequence (LED3) and a derivative (VR318) possessing a single base change to the wild-type nucleotide (U) at 2493 were used to determine the impact of the 2493 mutation on virus phenotype. The VP1 proteins of LED3 and VR318 viruses were distinguishable by denaturing electrophoretic analysis. LED3 produced smaller plaques in Vero cells than VR318 virus did. Neurovirulence testing of these cDNA-derived viruses in monkeys demonstrated that the 2493 mutation in LED3 virus is attenuating.
authors.affiliation: Lederle Laboratories, Pearl River, New York 10965.
authors.forename: J M
authors.initials: JM
authors.lastname: Tatem
authors.forename: C
authors.initials: C
authors.lastname: Weeks-Levy
authors.forename: A
authors.initials: A
authors.lastname: Georgiu
authors.forename: S J
authors.initials: SJ
authors.lastname: DiMichele
authors.forename: E J
authors.initials: EJ
authors.lastname: Gorgacz
authors.forename: V R
authors.initials: VR
authors.lastname: Racaniello
authors.forename: F R
authors.initials: FR
authors.lastname: Cano
authors.forename: S J
authors.initials: SJ
authors.lastname: Mento
mesh_terms: D000818:Animals; D002213:Capsid / Q000235:genetics*; D036022:Capsid Proteins; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011051:Poliomyelitis / Q000235:genetics*; D017955:Poliovirus / Q000235:genetics* / Q000472:pathogenicity; D014613:Vaccines, Attenuated; D014709:Vero Cells
chemical_list: D036022:Capsid Proteins; C442540:VP1 protein, Poliovirus; D014613:Vaccines, Attenuated