An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain.
The molecular basis of the temperature-sensitive (ts) phenotype of P3/Sabin, the type 3 vaccine strain of poliovirus, was investigated in light of the known correlation between ts and attenuation phenotypes. A phenylalanine at residue 91 of the capsid protein VP3 was a major determinant of both phenotypes, and attenuation and ts could be reverted by the same second-site mutations. The ts phenotype was due to a defect early in the assembly process that inhibited the formation of 14S pentamers, empty capsids, and virions. It was further shown that capsid proteins that were not incorporated into higher-order structures had short half-lives at the nonpermissive temperature.
Macadam
A J
AJ
National Institute for Biological Standards and Control, Hertfordshire, United Kingdom.
Ferguson
G
G
Arnold
C
C
Minor
P D
PD
D002213:Capsid / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D006801:Humans; D007700:Kinetics; D009154:Mutation; D010641:Phenotype; D017955:Poliovirus / Q000235:genetics* / Q000254:growth & development / Q000276:immunology; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D013696:Temperature; D014613:Vaccines, Attenuated
D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral; D014613:Vaccines, Attenuated