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http://purl.uniprot.org/citations/29093101http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29093101http://www.w3.org/2000/01/rdf-schema#comment"Infectious bursal disease virus (IBDV) is a bisegmented double-strand RNA (dsRNA) virus of the Birnaviridae family. While IBDV genomic dsRNA lacks a 5' cap, the means by which the uncapped IBDV genomic RNA is translated effectively is unknown. In this study, we describe a cap-independent pathway of translation initiation of IBDV uncapped RNA that relies on VP1 and VP3. We show that neither purified IBDV genomic dsRNA nor the uncapped viral plus-sense RNA transcripts were directly translated and rescued into infectious viruses in host cells. This defect in translation of the uncapped IBDV genomic dsRNA was rescued by trans-supplementation of the viral proteins VP1 and VP3 which was dependent on both the intact polymerase activity of VP1 and the dsRNA binding activity of VP3. Deletion analysis showed that both 5' and 3' untranslated regions (UTRs) of IBDV dsRNA were essential for VP1/VP3-dependent translation initiation. Significantly, VP1 and VP3 could also mediate the recovery of infectious IBDV from the authentic minus-sense strand of IBDV dsRNA. Moreover, downregulation or inhibition of the cap-binding protein eIF4E did not decrease but, rather, enhanced the VP1/VP3-mediated translation of the uncapped IBDV RNA. Collectively, our findings for the first time reveal that VP1 and VP3 compensate for the deficiency of the 5' cap and replace eIF4E to confer upon the uncapped IBDV RNA the ability to be translated and rescued into infectious viruses.IMPORTANCE A key point of control for virus replication is viral translation initiation. The current study shows that the uncapped IBDV RNA cannot be translated into viral proteins directly by host translation machinery and is thus noninfectious. Our results constitute the first direct experimental evidence that VP1 and VP3 are required and sufficient to initiate translation of uncapped IBDV genomic RNA by acting as a substitute for cap and replacing the cap-binding protein eIF4E. Significantly, VP1/VP3 mediate the recovery of infectious IBDV not only from the plus-sense strand but also from the minus-sense strand of the IBDV dsRNA. These findings provide not only new insights into the molecular mechanisms of the life cycle of IBDV but also a new tool for an alternative strategy for the recovery of IBDV from both the plus- and the minus-sense strands of the viral genomic dsRNA."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.org/dc/terms/identifier"doi:10.1128/jvi.01345-17"xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Han X."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Liu H."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Wang Y."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Yu Z."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Ye C."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/author"Zhang E."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/name"J Virol"xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/pages"e01345-17"xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/title"VP1 and VP3 Are Required and Sufficient for Translation Initiation of Uncapped Infectious Bursal Disease Virus Genomic Double-Stranded RNA."xsd:string
http://purl.uniprot.org/citations/29093101http://purl.uniprot.org/core/volume"92"xsd:string
http://purl.uniprot.org/citations/29093101http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29093101
http://purl.uniprot.org/citations/29093101http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29093101
http://purl.uniprot.org/uniprot/#_Q82630-mappedCitation-29093101http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29093101
http://purl.uniprot.org/uniprot/#_Q82635-mappedCitation-29093101http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29093101
http://purl.uniprot.org/uniprot/Q82635http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29093101
http://purl.uniprot.org/uniprot/Q82630http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/29093101