Table 1.
Viral miRNAs with regulatory functions and immune evasion approaches.
| Virus | v-miRNA | Target | Regulation/Immune evasion | Model | References |
|---|---|---|---|---|---|
| DNA virus family | |||||
| Herpesviruses | |||||
| HSV-1 | miR-H2-3p | ICP0, ICP4 | Immediate-early transactivation (latency establishment) |
Male CD-1 mice, 293T and Vero cells (Δ) | (79, 80) |
| miR-H3 | ICP34.5 | Neuro-virulence determinant | (Δ) | (79) | |
| miR-H4 | ICP34.5 | Neuro-virulence factor | (Δ) | (79) | |
| miR-H6 | ICP0, ICP4 | Immediate-early transactivation (latency establishment) |
(Δ) | (79, 80) | |
| miR-H8 | PIGT | GPI anchoring and immune evasion |
BJAB cells, NK cells |
(133) | |
| HSV-2 | miR-H2/H3/H4 | ICP0; ICP34.5 | Immediate-early transactivation (latency establishment); neuro-virulence determinant |
Vero, HEK293, HeLa, and US02 cells | (126, 127) |
| HCMV | miR-UL-112-1 | IE72 | Immediate-early transactivation (latency establishment) |
NHDF and U373 cells | (55, 63) |
| UL114 | Viral uracil DNA glycosylase | HFF cells | (62) | ||
| miR-UL-112-1, miR-US5-1, miR-US5-2 |
VAMP3; RAB5C;RAB11A; SNAP23; CDC42 |
Host secretary pathways; control cytokine secretion; formation of VAC |
NHDFs, HEK293 (VAMP3-FL-cDNA clone) |
(134) | |
| miR-UL-112-1 | MICB | Cell-mediated immunity by NK cell ligand |
Cells-HFF, RKO, DU145, PC3, 1106mel, NK cells | (67) | |
| miR-UL-112-1, miR-US5-1 |
IKKα; IKKβ | Blocks NFκB signaling; partially blocks IL-1β and TNFα signaling | NHDF, THP-1, hAECs | (54) | |
| miR-UL-148D-1 | RANTES | Activation and secretion of T cells, controls viral pathogenesis | HFF cells | (71) | |
| ACVR1B | Triggered secretion of IL-6, controls viral pathogenesis | HFFF2, CD34+ myeloid cells | (69) | ||
| miR-US4-1 | ERAP1, acts as biomarker |
Controls MHC-I presentation to CD8+ T cells, indicator of IFNα treatment in hepatitis B patients | Serum (Patient) | (135) | |
| EBV | miR-BART22 | LAMP2A | Viral oncogenesis in NPC and immune evasion | HEK293T cells, biopsy samples | (136) |
| NDRG1; IL12 |
Immune surveillance escape; T-cell differentiation, activation and recognition |
B95-8, PC-3 AdAH, HEK293, and C666-1 cells; hPBMCs, B cells, T cells and LCLs |
(137, 138) | ||
| miR-BART1-5p and miR-BART5-5p |
Viral LMP1 | Apoptotic inducer and transforming factor, viral oncogenesis | NPC cells | (128) | |
| miR-BART16 | LMP1 | Apoptotic inducer and transforming factor, viral oncogenesis | NPC cells | (128) | |
| TOMM2; CBP | Mitochondrial membrane protein; immunomodulation | B cells (DG75-eGFP and DG75-10/12) |
(139) | ||
| miR-BART17-5p | LMP1 | Apoptotic inducer and transforming factor, viral oncogenesis | NPC cells | (128) | |
| TAP2 | Peptide transportation | hPBMCs, B cells, T cells, and LCLs | (138) | ||
| miR-BART1 | IL12B; IFI30 |
T-cell differentiation, activation and recognition; antigen processing |
hPBMCs, B cells, T cells, and LCLs | (138) | |
| miR-BART2/BART2-5p (Viral) | BALF5 | DNA polymerization and controls viral replication | BL41 cells | (129) | |
| MICB; LGMN and CTSB; IL12B |
Cell-mediated immunity by NK cell ligand; antigen processing; T-cell differentiation, activation, and recognition | 293T, RKO, HeLa, 721.221 and BCBL1 cells; NK cells; hPBMCs, B cells, T cells, and LCLs |
(138, 140–142) | ||
| miR-BART3-3p | IPO7 | Nuclear import protein; T-cell activation and immune cell tolerance | B cells (DG75-eGFP and DG75-10/12) | (139) | |
| miR-BART5 | PUMA | Apoptotic inducer and proapoptotic factor | hNPC and EBV-GC cells | (143) | |
| miR-BART5-3p | TP53 | Cell cycle progression by inhibiting p53, inhibition of apoptosis | EBV-gastric cancer cell lines | (144) | |
| miR-BART8 | IFN-γ | Immunomodulation | YT, NK92, and Jurkat cells | (145) | |
| miR-BART10-3p | IL12B | T-cell differentiation, activation, and recognition | hPBMCs, B cells, T cells, and LCLs | (138) | |
| miR-BART11-5p | EBF1 | B-cell differentiation | B cells, LCLs, HEK293T | (146) | |
| miR-BART15 | NLRP3; BRUCE | Inflammasome production; apoptosis | Macrophages; AGS, SUN-719 cells | (147, 148) | |
| miR-BART16 | CBP | Immunomodulation | EBV+BL and SUN-719 cells | (149) | |
| miR-BART17 | TAP2 | Peptide transportation | hPBMCs, B cells, T cells, and LCLs | (138) | |
| miR-BART18-5p | MAP3K2 | Lytic reactivation | B cells | (150) | |
| miR-BART20-5p | BRLF1 and BZLF1 | Latency establishment | AGS, SUN-719, and YCCEL1 | (130) | |
| BAD; IFN-γ |
Apoptosis; immunomodulation |
AGS, SUN-719, YCCEL1, DG75, and B cells; YT, NK92, and Jurkat cells |
(145, 151) | ||
| miR-BHRF1-2 | PRDM1; CTSB; IL12B |
B-cell terminal differentiation; antigen processing; T-cell differentiation, activation, and recognition | LCLs, JY25, CCL156/159, TIB190, BL cells; hPBMCs, B cells, T cells and LCLs |
(138, 152) | |
| miR-BHRF1-3 | CXCL11; TAP2 |
Chemokine and T-cell attractant; peptide transportation | BL-5/8, EBV+BL, BC-1, JCS-1, and PEL cells; hPBMCs, B cells, T cells, and LCLs |
(138, 153) | |
| miR-BHRF1, miR-BHRF2, miR-BHRF3 |
BSAP1/pax5, RFX1, YY1, MIBP1, CREB, ATF1 | Cellular transactivator: regulate expression of Wp/Cp promoter; viral infection persistence | B cells | (154–156) | |
| KSHV | miR-K12-9*, miR-K12-5p, miR-K9*/miR-K5, miR-K12-7-5p |
RTA | Controls viral replication and transcriptional activator (latency establishment) |
HFF, BCBL-1, SLK, HEK293; DG75 and BCBL-1 cells; HEK293-Bac36 cells | (157, 158) |
| miR-Cluster | THBS1 EXOC6 ZNF684 CDK5RAP1 |
Inhibition of angiogenesis; SEC15 gene: Zinc figure protein; regulation of neural differentiation |
BCBL-1, HEK293; B cells (DG75-eGFP and DG75-10/12) | (139, 159) | |
| miR-K1, miR-K12-1 | P21; IκBα |
Inhibition of cell cycle; inhibits NFκB signaling |
U2OS, BL40, HEK293T, BC-3; PEL-BCP-1 cells |
(160–162) | |
| miR-K12-1, miR-K12-3p, miR-K12-6-3p | THBS1 | Cell cycle regulation and tumor suppression | BCBL-1, HEK293 | (159) | |
| miR-K12-1, miR-K12-3 | CASP3 | Inhibition of apoptosis | HEK293 and DG75 cells | (163) | |
| miR-K12-3 | NFIB | Latency establishment | BC-3 cells | (164) | |
| LRRC8D; NHP2L1 |
Activation of immune cells; U4 snRNA nuclear binding protein | B cells (DG75-eGFP and DG75-10/12) | (139) | ||
| miR-K12-3, miR-K12-7 | C/EBPβ (LIP) | Transcriptional activator | BCBL-1, MM6, and RAW cells | (165) | |
| miR-K12-4 | IκBα | Inhibits NFκB signaling | PEL-BCP-1 cells | (162) | |
| miR-K12-4-3p | GEMIN8; CASP3 |
Splicing factor; inhibition of apoptosis |
B cells (DG75-eGFP and DG75-10/12); HEK293 and DG75 cells |
(139, 163) | |
| miR-K12-4-5p | Rbl-2 | Rb-like protein | DMVECs, HEK293T | (131) | |
| miR-K12-5 | BCLAF1; Rbl-2 | Proapoptotic factor and promotes lytic reactivation; Rb-like protein | HUVEC, BCBL-1, BJAB-B cells; DMVECs, HEK293T |
(131, 166) | |
| miR-K12-6 | MAF | Transcription factor | LECs, BECs | (167) | |
| miR-K12-7 | MICB; NFIB | Cell-mediated immunity by NK cell ligand; latency establishment |
293T, RKO, HeLa, 721.221, and BCBL1 cells, and NK cells; BC-3 cells |
(140, 164) | |
| miR-K12-9 | IRAK1 and MyD88; BCLAF1 |
Immune evasion; proapoptotic factor and promotes lytic reactivation |
HEK293, SLK, HUVEC, BCBL-1, and BJAB-B cells |
(166, 168) | |
| miR-K12-10a/b | TWEAKR; BCLAF1 |
Regulates apoptosis and inflammation; proapoptotic factor and promotes lytic reactivation |
HUVEC, SLK+K cells; BCBL-1, BJAB-B cells |
(166, 169) | |
| miR-K12-11 ** identical seed sequence to that of cellular miR-155 | BACH1; C/EBPβ; MAF; IκBα; THSB1; NFIB |
Transcriptional suppressor; splenic B-cell expansion and induces lymphomagenesis; transcription factor; inhibits NFκB signaling; cell cycle regulation and tumor suppression; latency establishment |
BCP-1, BC-1, VG-1, JSC-1, RAJI, BCBL-1 BJAB; hCB cells, NOD/LtSz-scid IL2Rγnull mice; LECs, BECs; PEL-BCP-1 cells; BC-3 cells |
(162, 164, 167, 170–173) | |
| Polyomaviruses | |||||
| SV40 | miR-M1 (5p and 3p) | T Antigens (Large) | Regulation of early viral genes; transforming factor | TC-7/Db cells | (17) |
| SA12 | miR-S1 | T Antigens (Large) | Regulation of early viral genes | BSC40 cells | (105) |
| BKV | miR-B1 | T Antigens (Large) | Regulation of early viral genes | U87 and Vero cells | (104) |
| JCV | miR-J1 (5p and 3p) | T Antigens (Large) | Regulation of early viral genes; transforming factor | U87 and Vero cells | (104) |
| MCV | miR-S1 | T Antigens (Large) | Regulation of early viral genes | HEK293T cells and MCC350 plasmid | (103) |
| Hepadnavirus | |||||
| HBV | HBV-miR-3 | 3.4 kb viral transcript | Regulate HBc protein and pgRNA levels to alter viral replication | Huh7 and HepG2.2.15 cells | (90) |
| RNA virus family | |||||
| Orthomyxovirus | |||||
| Influenza | Engineered host miR-124 in intronic region of the virus | miR-124 targets | Regulate cellular functions of miR-124 | HEK293, MDCK, CAD, murine fibroblast | (110) |
| miR-HA-3p | PCBP2 | Regulates cytokine production and viral infection | in-vivo mouse model | (112) | |
| Filovirus | |||||
| EBoV | miR-1-3p, miR-1-5p, and miR-T3-3p | c-MET, Activin, and KPNA1 (by miR-155 ortholog) | Cellular signaling pathways, immune response dysregulation | Balb/c mice, NHP, and patients | (174) |
| Flaviviruses | |||||
| WNV | KUN-miR-1 | GATA4 | Regulates viral replication | Mosquito cells and bioinformatic approaches | (175) |
| DENV | DENV-vsRNA-5 | NS-1 | Autoregulation of viral replication | Mosquito cells and deep-sequencing approach | (176) |
| ZIKA | Putative 47 v-miRNAs | Multiple cellular targets | Immune surveillance and other biological pathways | Bioinformatic approaches | (177) |
| Picornavirus | |||||
| HAV | hav-miR-N1-3p | MAVS (in-silico predicted target) | Cellular antiviral pathways | KMB17 and HEK293T cells | (178) |
| Retrovirus | |||||
| HIV-I | miR-N367 | Nef | Persistence viral infection | Balb/c and C3H/Hej mice; Jurkat T and MT-4T cells |
(119) |
| miR-TAR-5p and miR-TAR-3p |
Multiple genes involved in apoptosis and cell survival | Apoptosis and viral propagation | Jurkat and J-LAT cells |
(179) | |
| miR-H3 | HIV-1 5′LTR | Enhances promoter activity and viral infection | Sup-T1, HEK293T, TZM-bl, and hPBMCs | (123) | |