Differences in replication of attenuated and neurovirulent polioviruses in human neuroblastoma cell line SH-SY5Y.
A base change from C to U at position 472 of the 5' noncoding region of the poliovirus genome is known to be a major determinant of attenuation in the P3/Sabin vaccine strain. To determine the biochemical basis for the attenuated phenotype imparted by this mutation, a cell line in which replication of neurovirulent and attenuated viruses could be distinguished was identified. A pair of P3/Sabin-P2/Lansing viral recombinants that differ only at position 472 was used; the viruses replicated equally well in HeLa cells, but the virus with a U at base 472 was attenuated in mice. In the human neuroblastoma cell line SH-SY5Y, recombinants with a U at base 472 replicated to approximately 10-fold-lower titers than did neurovirulent viruses with a C at this position. Analysis of viral RNA and protein synthesis indicated that translation of the attenuated viral RNA was specifically reduced in SH-SY5Y cells.
La Monica
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Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Racaniello
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D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D009447:Neuroblastoma / Q000382:microbiology; D009474:Neurons / Q000382:microbiology*; D017955:Poliovirus / Q000254:growth & development* / Q000472:pathogenicity*; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014613:Vaccines, Attenuated; D014764:Viral Proteins / Q000096:biosynthesis; D014779:Virus Replication
D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014764:Viral Proteins