Coupled mutations in the 5'-untranslated region of the Sabin poliovirus strains during in vivo passages: structural and functional implications

• Published in: Virus research Vol. 21; no. 2; p. 111
• Main Authors: Muzychenko, A R, Lipskaya GYu, Maslova, S V, Svitkin, Y V, Pilipenko, E V, Nottay, B K, Kew, O M, Agol, V I
• Format: Journal Article
• Language: English
• Published: Netherlands 01-10-1991
• Subjects: Base Sequence; Electrophoresis, Polyacrylamide Gel; Genes, Viral - genetics; Humans; Molecular Sequence Data; Mutagenesis; Nucleotides - genetics; Poliovirus - genetics; Poliovirus - growth & development; Poliovirus - isolation & purification; Poliovirus Vaccine, Oral - genetics; Protein Biosynthesis; RNA, Viral - genetics; Structure-Activity Relationship
• ISSN: 0168-1702
• DOI: 10.1016/0168-1702(91)90002-D

All entero- and rhinovirus RNAs sequenced thus far possess A and U residues at positions corresponding to nucleotides 480 and 525, respectively, of poliovirus type 1. These two nucleotides have been proposed previously to form a base pair. The single exception to this rule appears to be the Sabin type 1 strain, which has a G480. Isolates of the Sabin 1 virus from healthy vaccinees were shown to have either a reversion to A480 or a second-site mutation U525---C, both restoring a potential for efficient base pairing. In vitro translation experiments demonstrated that poliovirus type 1 RNAs with either A480-U525 or G480-C525 are more efficient in promoting translation initiation as compared with the Sabin 1 RNA (G480-U525). The Sabin 2 strain has a U and an A at position 398 and 481, respectively, while its predecessor, strain P712, is shown to have C398 and G481. All the derivatives of the Sabin 2 isolated from vaccine-associated paralytic poliomyelitis cases shown reversion to G481, and most of them reverted also to C398. It is proposed that bases at positions 398 and 481 may be involved in a tertiary interaction. The in vitro template activity of the Sabin type 2 RNA (A481) is significantly lower than that of the isolate RNAs with G481, thus confirming the relation between attenuation and translation efficiency demonstrated previously for the type 1 and type 3 Sabin strains. The C---U change at position 398 exerted only a minor effect on the RNA template activity.