title: Coordinated function of cellular DEAD-box helicases in suppression of viral RNA recombination and maintenance of viral genome integrity.
abstract: The intricate interactions between viruses and hosts include an evolutionary arms race and adaptation that is facilitated by the ability of RNA viruses to evolve rapidly due to high frequency mutations and genetic RNA recombination. In this paper, we show evidence that the co-opted cellular DDX3-like Ded1 DEAD-box helicase suppresses tombusviral RNA recombination in yeast model host, and the orthologous RH20 helicase functions in a similar way in plants. In vitro replication and recombination assays confirm the direct role of the ATPase function of Ded1p in suppression of viral recombination. We also present data supporting a role for Ded1 in facilitating the switch from minus- to plus-strand synthesis. Interestingly, another co-opted cellular helicase, the eIF4AIII-like AtRH2, enhances TBSV recombination in the absence of Ded1/RH20, suggesting that the coordinated actions of these helicases control viral RNA recombination events. Altogether, these helicases are the first co-opted cellular factors in the viral replicase complex that directly affect viral RNA recombination. Ded1 helicase seems to be a key factor maintaining viral genome integrity by promoting the replication of viral RNAs with correct termini, but inhibiting the replication of defective RNAs lacking correct 5' end sequences. Altogether, a co-opted cellular DEAD-box helicase facilitates the maintenance of full-length viral genome and suppresses viral recombination, thus limiting the appearance of defective viral RNAs during replication.
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Chingkai
authors.initials: C
authors.lastname: Chuang
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: K Reddisiva
authors.initials: KR
authors.lastname: Prasanth
authors.affiliation: Department of Plant Pathology, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Nagy
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005095:Exoribonucleases / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D018749:RNA, Plant / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D014026:Nicotiana / Q000235:genetics / Q000821:virology*; D017864:Tombusvirus / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D010940:Plant Proteins; D018749:RNA, Plant; D012367:RNA, Viral; D029701:Saccharomyces cerevisiae Proteins; D012324:RNA-Dependent RNA Polymerase; D005095:Exoribonucleases; C068398:XRN1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; C492152:DED1 protein, S cerevisiae; D053487:DEAD-box RNA Helicases