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The physiological RIG-I ligands produced during IAV infection are not fully elucidated. Cellular constraints leading to the inhibition of ongoing viral replication likely potentiate an erroneous viral polymerase producing aberrant viral RNA species activating RIG-I. Here, we demonstrate that RIG-I activation during chemical inhibition of continuous viral protein synthesis is attributable to the incoming DI genomes. Erroneous viral replication driven by NP deprivation promotes the generation of RIG-I-activating aberrant viral RNA, but their nature is likely to be distinct from that of DI RNA. Our results thus reveal distinct mechanisms of RIG-I activation by IAV under cellular constraints impeding ongoing viral replication. A better understanding of RIG-I sensing of IAV infection provides insight into the development of novel interventions to combat influenza virus infection.<\/jats:p>","DOI":"10.1128\/jvi.02066-18","type":"journal-article","created":{"date-parts":[[2019,1,3]],"date-time":"2019-01-03T13:18:25Z","timestamp":1546521505000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Inhibition of Ongoing Influenza A Virus Replication Reveals Different Mechanisms of RIG-I Activation"],"prefix":"10.1128","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2520-7625","authenticated-orcid":false,"given":"GuanQun","family":"Liu","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Vaccinology and Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1508-7172","authenticated-orcid":false,"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Vaccinology and Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4706-1543","authenticated-orcid":false,"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Vaccinology and Immunotherapeutics Program, School of Public Health, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"},{"name":"Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-08"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01080-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04734"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.05.003"},{"key":"e_1_3_3_6_2","first-page":"1151","volume-title":"Fields Virology","author":"Shaw ML","year":"2013","unstructured":"Shaw ML, Palese P. 2013. 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