Cell-dependent role for the poliovirus 3' noncoding region in positive-strand RNA synthesis.
We previously reported the isolation of a mutant poliovirus lacking the entire genomic RNA 3' noncoding region. Infection of HeLa cell monolayers with this deletion mutant revealed only a minor defect in the levels of viral RNA replication. To further analyze the consequences of the genomic 3' noncoding region deletion, we examined viral RNA replication in a neuroblastoma cell line, SK-N-SH cells. The minor genomic RNA replication defect in HeLa cells was significantly exacerbated in the SK-N-SH cells, resulting in a decreased capacity for mutant virus growth. Analysis of the nature of the RNA replication deficiency revealed that deleting the poliovirus genomic 3' noncoding region resulted in a positive-strand RNA synthesis defect. The RNA replication deficiency in SK-N-SH cells was not due to a major defect in viral translation or viral protein processing. Neurovirulence of the mutant virus was determined in a transgenic mouse line expressing the human poliovirus receptor. Greater than 1,000 times more mutant virus was required to paralyze 50% of inoculated mice, compared to that with wild-type virus. These data suggest that, together with a cellular factor(s) that is limiting in neuronal cells, the poliovirus 3' noncoding region is involved in positive-strand synthesis during genome replication.
Brown
David M
DM
Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697, USA.
Kauder
Steven E
SE
Cornell
Christopher T
CT
Jang
Gwendolyn M
GM
Racaniello
Vincent R
VR
Semler
Bert L
BL
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017353:Gene Deletion; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D009447:Neuroblastoma; D011051:Poliomyelitis / Q000503:physiopathology / Q000821:virology*; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000096:biosynthesis*; D011991:Receptors, Virus / Q000235:genetics; D014407:Tumor Cells, Cultured; D014774:Virulence; D014779:Virus Replication
D020413:3' Untranslated Regions; D008565:Membrane Proteins; D012367:RNA, Viral; D011991:Receptors, Virus; C066100:poliovirus receptor