Rebecca Skalsky (Oregon Health and Science University, USA)
“Regulation of Host Signaling Pathways by EBV miRNAs”
EBV encodes 25 precursor miRNAs
~100-200 different target sites on mRNAs
> 44 EBV miRNAs =significan tregulatory potential
MiRNAs are great toools for viruses:
– non-immunogenicity
– -require limited encoding capacity (only 22 not)
-can rapidly evolve; have
Lymphocryptoivirus muRNAs are highly conserves
Circular acting, extra-cellular LCV miRNAs in SV+ monkeys
EBV miRNA expression (~30% of miRNAs are viral)
MRSeq analysis:
BART19 SNPs? Steady state miRNA levels = miRNA biogenesis + miRNA turnover (targetome)
What do EBV miRNAs target
– PAR-CLIP. Hi resolution “Blue-prin” of the miRNA targetome
Capture ~25000 miRNA:mRNA interactions (>30% are in 3’UTR; ~20
LMP1 is regulated by five EBV BART miRs
(Lo 2007; Stalsky, 2012; Riley, 201; Skalsky, 2014; Verhoeven, 2016)_
EBV miRs impact LMP1 function miRNA BART3 targets NFKB signaling pathway
Imbalances in miRNA regulation of LMP1 might be a
Prioritizing cell signaling pathways regulated by EBV miRNAs
Meta-analysis of PARCLIP datasets:
840 3’UTR
EBV miRNAs regulate IL1 signaling
Several EBV miRNAs moderately reduce NFKB activation , nut only BHRF1-2 and BAT11 are significant
IL1R1 is regulated by EBV miR-BHRF1-2-5p.
Activity of miR-BHRF1-2-5p regulates IL-1Blocker responsiveness in EBV infected B cells
Reduce recruitment of immune effector cells? Lower IFNG and T cell respond
EBV miRNAs regulate signaling through growth factor receptors
EBV neg BJAB-luc cells
Signaling through the BCR.
— shRNAs pheocopy EBV miRNA activity
– In common RAC1,
Antagonize balance LMP2A activities
EENV miRNAs impact lytic deactivation
——miRNA-141 is induced in MutuI cells by BCR x-linking
— miR-141 and EBV miR-BART9 enhance BZLF1 promoter activity