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To further analyze the consequences of the genomic 3\u2032 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\u2032 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\u2032 noncoding region is involved in positive-strand synthesis during genome replication.<\/jats:p>","DOI":"10.1128\/jvi.78.3.1344-1351.2004","type":"journal-article","created":{"date-parts":[[2004,1,13]],"date-time":"2004-01-13T16:28:00Z","timestamp":1074011280000},"page":"1344-1351","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Cell-Dependent Role for the Poliovirus 3\u2032 Noncoding Region in Positive-Strand RNA Synthesis"],"prefix":"10.1128","volume":"78","author":[{"given":"David M.","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Kauder","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 00858"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher T.","family":"Cornell","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn M.","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent R.","family":"Racaniello","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 00858"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert L.","family":"Semler","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, College of Medicine, University of California, Irvine, California 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1030"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(85)90386-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.63.9.4034-4038.1989"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(84)90246-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90170-J"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.6.1439"},{"key":"e_1_3_2_8_2","unstructured":"Bodian D. and D. 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