Rebecca Skalsky

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