# Systematic Genome-wide Screening and Prediction of microRNAs in EBOV During the 2014 Ebolavirus Outbreak

**Authors:** Yue Teng, Yuzhuo Wang, Xianglilan Zhang, Wenli Liu, Hang Fan, Hongwu Yao, Baihan Lin, Ping Zhu, Wenjun Yuan, Yigang Tong, Wuchun Cao

PMC · DOI: 10.1038/srep09912 · 2015-05-26

## TL;DR

This study identifies potential microRNAs in the 2014 Ebolavirus outbreak genome and suggests they may help the virus evade host defenses.

## Contribution

The first genome-wide prediction of ebolavirus microRNAs and their potential roles in host immune evasion during the 2014 outbreak.

## Key findings

- Four putative viral pre-miRNAs and seven mature miRNAs were predicted in the Ebolavirus genome.
- Ebola miRNAs may silence genes like NFKBIE and RIPK1, which are involved in host defense mechanisms.
- The virus may use miRNAs to inhibit NF-kB and TNF pathways, aiding in immune evasion and virus spread.

## Abstract

Recently, several thousand people have been killed by the Ebolavirus disease (EVD) in West Africa, yet no current antiviral medications and treatments are available. Systematic investigation of ebolavirus whole genomes during the 2014 outbreak may shed light on the underlying mechanisms of EVD development. Here, using the genome-wide screening in ebolavirus genome sequences, we predicted four putative viral microRNA precursors (pre-miRNAs) and seven putative mature microRNAs (miRNAs). Combing bioinformatics analysis and prediction of the potential ebolavirus miRNA target genes, we suggest that two ebolavirus coding possible miRNAs may be silence and down-regulate the target genes NFKBIE and RIPK1, which are the central mediator of the pathways related with host cell defense mechanism. Additionally, the ebolavirus exploits the miRNAs to inhibit the NF-kB and TNF factors to evade the host defense mechanisms that limit replication by killing infected cells, or to conversely trigger apoptosis as a mechanism to increase virus spreading. This is the first study to use the genome-wide scanning to predict microRNAs in the 2014 outbreak EVD and then to apply systematic bioinformatics to analyze their target genes. We revealed a potential mechanism of miRNAs in ebolavirus infection and possible therapeutic targets for Ebola viral infection treatment.

## Linked entities

- **Genes:** NFKBIE (NFKB inhibitor epsilon) [NCBI Gene 4794], RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737]
- **Diseases:** Ebolavirus disease (MONDO:0005737)

## Full-text entities

- **Genes:** EGFLAM (EGF like, fibronectin type III and laminin G domains) [NCBI Gene 133584] {aka AGRINL, AGRNL, PIKA}, ADRA2B (adrenoceptor alpha 2B) [NCBI Gene 151] {aka ADRA2L1, ADRA2RL1, ADRARL1, ALPHA2BAR, FAME2, alpha-2BAR}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, ARFGEF3 (ARFGEF family member 3) [NCBI Gene 57221] {aka A7322, BIG3, C6orf92, KIAA1244, PPP1R33, dJ171N11.1}, NFKBIE (NFKB inhibitor epsilon) [NCBI Gene 4794] {aka IKBE}, HDAC5 (histone deacetylase 5) [NCBI Gene 10014] {aka HD5, NY-CO-9}, Crys (Crystallin) [NCBI Gene 34604] {aka CG16963, Cry, Dcy, DmelCry, Dmel\CG16963, c}, TMEM63A (transmembrane protein 63A) [NCBI Gene 9725] {aka HLD19, KIAA0792, hTMEM63A}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, PRKAB2 (protein kinase AMP-activated non-catalytic subunit beta 2) [NCBI Gene 5565], MIXL1 (Mix paired-like homeobox) [NCBI Gene 83881] {aka MILD1, MIX, MIXL}, PTPRT (protein tyrosine phosphatase receptor type T) [NCBI Gene 11122] {aka R-PTP-T, RPTP-rho, RPTPrho}, ADGRG2 (adhesion G protein-coupled receptor G2) [NCBI Gene 10149] {aka CBAVDX, EDDM6, GPR64, HE6, TM7LN2}, SHTN1 (shootin 1) [NCBI Gene 57698] {aka KIAA1598, shootin-1}, S100A10 (S100 calcium binding protein A10) [NCBI Gene 6281] {aka 42C, ANX2L, ANX2LG, CAL1L, CLP11, Ca[1]}, EFNA3 (ephrin A3) [NCBI Gene 1944] {aka EFL2, EPLG3, Ehk1-L, LERK3}, NPLOC4 (NPL4 homolog, ubiquitin recognition factor) [NCBI Gene 55666] {aka NPL4}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, WASF2 (WASP family member 2) [NCBI Gene 10163] {aka IMD2, SCAR2, WASF4, WAVE2, dJ393P12.2}, ADTRP (androgen dependent TFPI regulating protein) [NCBI Gene 84830] {aka AIG1L, C6orf105, dJ413H6.1}, GMEB2 (glucocorticoid modulatory element binding protein 2) [NCBI Gene 26205] {aka GMEB-2, P79PIF, PIF79}, THOC3 (THO complex subunit 3) [NCBI Gene 84321] {aka THO3, hTREX45}, LINC03124 (long intergenic non-protein coding RNA 3124) [NCBI Gene 29798] {aka C2orf27, C2orf27A, C2orf27B}, ARHGAP27 (Rho GTPase activating protein 27) [NCBI Gene 201176] {aka CAMGAP1, PP905, SH3D20, SH3P20}, GNAT1 (G protein subunit alpha transducin 1) [NCBI Gene 2779] {aka CSNB1G, CSNBAD3, GBT1, GNATR, HG1F}, DROSHA (drosha ribonuclease III) [NCBI Gene 29102] {aka ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN}, GCOM1 (GCOM1, MYZAP-POLR2M combined locus) [NCBI Gene 145781] {aka GRINL1A, Gcom2, MYZAP-POLR2M, gcom}, ARFIP1 (ARF interacting protein 1) [NCBI Gene 27236] {aka HSU52521}, MTMR6 (myotubularin related protein 6) [NCBI Gene 9107], CFTR (CF transmembrane conductance regulator) [NCBI Gene 1080] {aka ABC35, ABCC7, CF, CFTR/MRP, MRP7, TNR-CFTR}, JARID2 (jumonji and AT-rich interaction domain containing 2) [NCBI Gene 3720] {aka DIDDF, JMJ}, JAML (junction adhesion molecule like) [NCBI Gene 120425] {aka AMICA, AMICA1, CREA7-1, CREA7-4, Gm638}, VPS37B (VPS37B subunit of ESCRT-I) [NCBI Gene 79720], RABEP1 (rabaptin, RAB GTPase binding effector protein 1) [NCBI Gene 9135] {aka RAB5EP, RABPT5}, CCND2 (cyclin D2) [NCBI Gene 894] {aka KIAK0002, MPPH3}, UTS2B (urotensin 2B) [NCBI Gene 257313] {aka U-IIB, U2B, UIIB, URP, UTS2D}, AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, CYB561 (cytochrome b561) [NCBI Gene 1534] {aka CGCytb, CYB561A1, FRRS2, ORTHYP2}, ABCC1 (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) [NCBI Gene 4363] {aka ABC29, ABCC, DFNA77, GS-X, MRP, MRP1}, ELOVL2 (ELOVL fatty acid elongase 2) [NCBI Gene 54898] {aka SSC2}, MAPKAPK3 (MAPK activated protein kinase 3) [NCBI Gene 7867] {aka 3PK, MAPKAP-K3, MAPKAP3, MAPKAPK-3, MDPT3, MK-3}, XDH (xanthine dehydrogenase) [NCBI Gene 7498] {aka XAN1, XDH/XO, XO, XOR}, USP45 (ubiquitin specific peptidase 45) [NCBI Gene 85015] {aka LCA19}, NLGN4X (neuroligin 4 X-linked) [NCBI Gene 57502] {aka ASPGX2, AUTSX2, HLNX, HNL4X, NLGN4}, RNF31 (ring finger protein 31) [NCBI Gene 55072] {aka HOIP, IMD115, Paul, ZIBRA}, DCLK2 (doublecortin like kinase 2) [NCBI Gene 166614] {aka CL2, CLICK-II, CLICK2, CLIK2, DCAMKL2, DCDC3}, RNF185 (ring finger protein 185) [NCBI Gene 91445], BEST4 (bestrophin 4) [NCBI Gene 266675] {aka VMD2L2}, WFIKKN2 (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2) [NCBI Gene 124857] {aka GASP-1, WFDC20B, WFIKKNRP, hGASP-1}, GRB10 (growth factor receptor bound protein 10) [NCBI Gene 2887] {aka GRB-IR, Grb-10, IRBP, MEG1, RSS}, HES3 (hes family bHLH transcription factor 3) [NCBI Gene 390992] {aka bHLHb43}, RIPK1 (receptor interacting serine/threonine kinase 1) [NCBI Gene 8737] {aka AIEFL, IMD57, RIP, RIP-1, RIP1}, GTPBP1 (GTP binding protein 1) [NCBI Gene 9567] {aka GP-1, GP1, HSPC018, NEDFET1}, RHBDL1 (rhomboid like 1) [NCBI Gene 9028] {aka RHBDL, RRP}, MRE11 (MRE11 double strand break repair nuclease) [NCBI Gene 4361] {aka ATLD, HNGS1, MRE11A, MRE11B}, UPP1 (uridine phosphorylase 1) [NCBI Gene 7378] {aka UDRPASE, UP, UPASE, UPP}, MVB12B (multivesicular body subunit 12B) [NCBI Gene 89853] {aka C9orf28, FAM125B}, ENDOU (endonuclease, poly(U) specific) [NCBI Gene 8909] {aka P11, PP11, PRSS26}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}
- **Diseases:** MODS (MESH:D009102), congestive heart failure (MESH:D006333), infection (MESH:D007239), hemorrhagic fever (MESH:D006480), Inflammation (MESH:D007249), dystrophia myotonica (MESH:D009223), Edema (MESH:D004487), Ebola viral infection (MESH:D014777), hepatorenal syndrome (MESH:D006530), EVD (MESH:D019142)
- **Chemicals:** Purine (MESH:C030985), CO2 (MESH:D002245), SYBR Green (MESH:C098022), oligonucleotides (MESH:D009841), argon (MESH:D001128), DMEM (-), TRIzol (MESH:C411644)
- **Species:** Ebolavirus [taxon 186536], Ebola virus (no rank) [taxon 1570291], Hepatovirus A (no rank) [taxon 12092], Arabidopsis thaliana (mouse-ear cress, species) [taxon 3702], Hepatitis B virus (no rank) [taxon 10407], Mus musculus (house mouse, species) [taxon 10090], Human T-cell leukemia virus type I (no rank) [taxon 11908], Drosophila melanogaster (fruit fly, species) [taxon 7227], Dengue virus (no rank) [taxon 12637], Human immunodeficiency virus (species) [taxon 12721], HCV [taxon 11103], Zaire ebolavirus (no rank) [taxon 186538], Human immunodeficiency virus 1 (no rank) [taxon 11676], West Nile virus (no rank) [taxon 11082], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** Hela — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030)

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4603304/full.md

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Source: https://tomesphere.com/paper/PMC4603304