Abstract
ABSTRACT Many viral suppressors (VSRs) counteract antiviral RNA silencing, a central component of the plant’s immune response by sequestration of virus-derived antiviral small interfering RNAs (siRNAs). Here, we addressed how VSRs affect the activities of cellular microRNAs (miRNAs) during a viral infection by characterizing the interactions of two unrelated VSRs, the Tombusvirus p19 and the Cucumovirus 2b, with miRNA 162 (miR162), miR168, and miR403. These miRNAs regulate the expression of the important silencing factors Dicer-like protein 1 (DCL1) and Argonaute proteins 1 and 2 (AGO1 and AGO2), respectively. Interestingly, while the two VSRs showed similar binding profiles, the miRNAs were bound with significantly different affinities, for example, with the affinity of miR162 greatly exceeding that of miR168. In vitro silencing experiments revealed that p19 and 2b affect miRNA-mediated silencing of the DCL1 , AGO1 , and AGO2 mRNAs in strict accordance with the VSR’s miRNA-binding profiles. In Tombusvirus -infected plants, the miRNA-binding behavior of p19 closely corresponded to that in vitro . Most importantly, in contrast to controls with a Δp19 virus, infections with wild-type (wt) virus led to changes of the levels of the miRNA-targeted mRNAs, and these changes correlated with the miRNA-binding preferences of p19. This was observed exclusively in the early stage of infection when viral genomes are proposed to be susceptible to silencing and viral siRNA (vsiRNA) concentrations are low. Accordingly, our study suggests that differential binding of miRNAs by VSRs is a widespread viral mechanism to coordinately modulate cellular gene expression and the antiviral immune response during infection initiation. IMPORTANCE Plant viruses manipulate their hosts in various ways. Viral suppressor proteins (VSRs) interfere with the plant’s immune response by sequestering small, antivirally acting vsiRNAs, which are processed from viral RNAs during the plant’s RNA-silencing response. Here, we examined the effects of VSRs on cellular microRNAs (miRNAs), which show a high degree of similarity with vsiRNAs. Binding experiments with two unrelated VSRs and three important regulatory miRNAs revealed that the proteins exhibit similar miRNA-binding profiles but bind different miRNAs at considerably different affinities. Most interestingly, experiments in plants showed that in the early infection phase, the Tombusvirus VSR p19 modulates the activity of these miRNAs on their target mRNAs very differently and that this differential regulation strictly correlates with the binding affinities of p19 for the respective miRNAs. Our data suggest that VSRs may specifically control plant gene expression and the early immune response by differential sequestration of miRNAs.
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Claims 9
Claim · model-written summary
The two viral suppressors had similar miRNA binding profiles.
Not reportedTaxon
Verbatim
e0“the two VSRs showed similar binding profiles”
Claim · model-written summary
miRNAs bound the suppressors with significantly different affinities.
Not reportedTaxon
Verbatim
e0“the miRNAs were bound with significantly different affinities”
Claim · model-written summary
miR162 binding affinity greatly exceeded miR168 affinity.
Not reportedTaxon
Verbatim
e0“the affinity of miR162 greatly exceeding that of miR168”
Claim · model-written summary
p19 and 2b affected silencing of DCL1, AGO1 and AGO2 mRNAs according to their binding profiles in vitro.
- Gene
- DCL1 , AGO1 , and AGO2 mRNAse0
- Outcome
- miRNA-mediated silencinge0
- Qualifier
- in strict accordance with the VSR’s miRNA-binding profilese0
Not reportedTaxonDirection
Verbatim
e0“p19 and 2b affect miRNA-mediated silencing of the DCL1 , AGO1 , and AGO2 mRNAs in strict accordance with the VSR’s miRNA-binding profiles”
Claim · model-written summary
p19 binding behavior in infected plants closely matched in vitro behavior.
- Taxon
- plantsViridiplantaee0
- Interactor
- TombusvirusTombusviruse0pathogen
- Gene
- p19e0
- Outcome
- miRNA-binding behaviore0
Not reportedDirection
Verbatim
e0“In Tombusvirus -infected plants, the miRNA-binding behavior of p19 closely corresponded to that in vitro”
Claim · model-written summary
Wild-type virus infection changed levels of miRNA-targeted mRNAs compared with Δp19 virus.
Not reportedTaxonDirection
Verbatim
e0“in contrast to controls with a Δp19 virus, infections with wild-type (wt) virus led to changes of the levels of the miRNA-targeted mRNAs”
Claim · model-written summary
The mRNA changes correlated with p19 miRNA binding preferences.
Not reportedTaxonDirection
Verbatim
e0“these changes correlated with the miRNA-binding preferences of p19”
Claim · model-written summary
The infection effects occurred exclusively in the early stage.
Not reportedTaxonDirection
Verbatim
e0“This was observed exclusively in the early stage of infection”
Claim · model-written summary
Authors suggest differential miRNA binding by viral suppressors modulates gene expression and early antiviral immunity.
- Gene
- miRNAse0
- Outcome
- cellular gene expression and the antiviral immune responsee0
- Qualifier
- during infection initiatione0
Not reportedTaxon
Verbatim
e0“differential binding of miRNAs by VSRs is a widespread viral mechanism to coordinately modulate cellular gene expression and the antiviral immune response during infection initiation”