Coupled mutations in the 5'-untranslated region of the Sabin poliovirus strains during in vivo passages: structural and functional implications.
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.
Muzychenko
A R
AR
Institute of Poliomyelitis and Viral Encephalitides, USSR Academy of Medical Sciences, Moscow.
Lipskaya GYu
Maslova
S V
SV
Svitkin
Y V
YV
Pilipenko
E V
EV
Nottay
B K
BK
Kew
O M
OM
Agol
V I
VI
D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005814:Genes, Viral / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009711:Nucleotides / Q000235:genetics; D017955:Poliovirus / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D011055:Poliovirus Vaccine, Oral / Q000235:genetics*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics*; D013329:Structure-Activity Relationship
D009711:Nucleotides; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral