title: Deep sequencing analysis of defective genomes of parainfluenza virus 5 and their role in interferon induction.
abstract: Preparations of parainfluenza virus 5 (PIV5) that are potent activators of the interferon (IFN) induction cascade were generated by high-multiplicity passage in order to accumulate defective interfering virus genomes (DIs). Nucleocapsid RNA from these virus preparations was extracted and subjected to deep sequencing. Sequencing data were analyzed using methods designed to detect internal deletion and "copyback" DIs in order to identify and characterize the different DIs present and to approximately quantify the ratio of defective to nondefective genomes. Trailer copybacks dominated the DI populations in IFN-inducing preparations of both the PIV5 wild type (wt) and PIV5-VΔC (a recombinant virus that does not encode a functional V protein). Although the PIV5 V protein is an efficient inhibitor of the IFN induction cascade, we show that nondefective PIV5 wt is unable to prevent activation of the IFN response by coinfecting copyback DIs due to the interfering effects of copyback DIs on nondefective virus protein expression. As a result, copyback DIs are able to very rapidly activate the IFN induction cascade prior to the expression of detectable levels of V protein by coinfecting nondefective virus.
authors: School of Biology, Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, United Kingdom.
authors: M J
authors: MJ
authors: Killip
authors: D F
authors: DF
authors: Young
authors: D
authors: D
authors: Gatherer
authors: C S
authors: CS
authors: Ross
authors: J A L
authors: JA
authors: Short
authors: A J
authors: AJ
authors: Davison
authors: S
authors: S
authors: Goodbourn
authors: R E
authors: RE
authors: Randall
mesh_terms: D000818:Animals; D002460:Cell Line; D003673:Defective Viruses / Q000235:genetics*; D016679:Genome, Viral; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007372:Interferons / Q000235:genetics / Q000276:immunology; D019213:Rubulavirus / Q000235:genetics*; D019351:Rubulavirus Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics
chemical_list: D014764:Viral Proteins; D007372:Interferons