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Although interactions with host innate and adaptive responses are complex and persistence mechanisms likely multi-factorial, we previously observed associations between bioinformatically predicted RNA secondary formation in genomes of positive-stranded RNA viruses with their in vivo fitness and persistence. To analyse this interactions functionally, we transfected fibroblasts with non-replicating, non-translated RNA transcripts from RNA viral genomes with differing degrees of genome-scale ordered RNA structure (GORS). Single-stranded RNA transcripts induced interferon-\u03b2 mediated though RIG-I and PKR activation, the latter associated with rapid induction of antiviral stress granules. A striking inverse correlation was observed between induction of both cellular responses with transcript RNA structure formation that was independent of both nucleotide composition and sequence length. The consistent inability of cells to recognize RNA transcripts possessing GORS extended to downstream differences from unstructured transcripts in expression of TNF-\u03b1, other interferon-stimulated genes and induction of apoptosis. This functional association provides novel insights into interactions between virus and host early after infection and provides evidence for a novel mechanism for evading intrinsic and innate immune responses.<\/jats:p>","DOI":"10.1093\/nar\/gkt1291","type":"journal-article","created":{"date-parts":[[2013,12,15]],"date-time":"2013-12-15T01:21:28Z","timestamp":1387070488000},"page":"3314-3329","source":"Crossref","is-referenced-by-count":49,"title":["The influence of viral RNA secondary structure on interactions with innate host cell defences"],"prefix":"10.1093","volume":"42","author":[{"given":"Jeroen","family":"Witteveldt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Blundell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris J.","family":"Maarleveld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"McFadden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,12,13]]},"reference":[{"key":"2019070602232515200_gkt1291-B1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.tig.2007.04.004","article-title":"A call to arms: coevolution of animal viruses and host innate immune responses","volume":"23","author":"Marques","year":"2007","journal-title":"Trends Genet."},{"key":"2019070602232515200_gkt1291-B2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1099\/vir.0.83391-0","article-title":"Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures","volume":"89","author":"Randall","year":"2008","journal-title":"J. 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