The?nonsense-mediated?decay?(NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus?Pea?enation?mosaic?virus?2?(PEMV2) is a nonsegmented, positive-sense RNA?virus?with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2?long-distance?movement?protein?p26 was previously shown to both stabilize?viral?RNAs and bind them for transport through the plant's vascular system. The current study demonstrated that p26?protects?both?viral?and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclu... More
The?nonsense-mediated?decay?(NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3' untranslated regions (UTRs). The umbravirus?Pea?enation?mosaic?virus?2?(PEMV2) is a nonsegmented, positive-sense RNA?virus?with an unusually long 3' UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2?long-distance?movement?protein?p26 was previously shown to both stabilize?viral?RNAs and bind them for transport through the plant's vascular system. The current study demonstrated that p26?protects?both?viral?and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of?long-distance?movement. Using a transcriptome-wide approach in the model plant?Nicotiana benthamiana, p26 protected a subset of cellular NMD target?transcripts, particularly those containing long, structured, GC-rich 3' UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the?host?transcriptome are common during plant RNA?virus?infections, and these results suggest that, in at least some instances,?virus-mediated NMD inhibition may be a major contributing factor.IMPORTANCE?Nonsense-mediated?decay?(NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3' untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in?host?cells. A?protein?required for?long-distance?movement?of?Pea?enation?mosaicvirus?2?(PEMV2) is shown to also protect both?viral?and?host?mRNAs from NMD. RNA-seq analyses of the?Nicotiana benthamianatranscriptome revealed that PEMV2 infection significantly impairs the?host?NMD pathway. RNA viruses routinely induce large-scale changes in?host?gene expression, and, like PEMV2, may use NMD inhibition to alter the?host?transcriptome in an effort to increase?virus?amplification.
