Table 1 Virus-mediated regulation of inflammation by host and viral microRNAs

miR-145-5p/

Down

IAV (H3N2)

In vitro (pHBEC)

-

Inhibition of inflammation

MiR-145-5p suppressed the NF-κB pathway, IL-1β and TNF-α expression during IAV infection.

LncRNA TUG1 was upregulated in pHBECs cells infected with IAV, leading lead to airway inflammation by sponging miR-145-5p.

[67]

miR‑221/ Down

IAV (H1N1)

In vitro (A549)

SOCS1

Inhibition of inflammation

MiR-146a/b expression has been substantially decreased within IAV‑infected A549 cells.

[68]

miR-4485/ Down

IAV

In vitro (A549)

STAT3

Inhibition of inflammation

H1N1 infection downregulated miR-4485 in A549 cells, while overexpression of miR-4485 ameliorated A549 cell damage caused by H1N1 by inhibiting apoptosis, decreasing IL-6, TNF-α & IL-1β and increasing cell viability.

[61]

miR-590-5p/ Up

IAV (H3N2)

In vitro (A549)

IL-6R

Inhibition of inflammation

miR-590-5p contributed to IAV replication by suppressing IL-6 and interferons.

[69]

miR-302a/ Down

IAV

Human (throat swabs), In vitro

IRF-5

Inhibition of inflammation

miR-302a suppressed IAV-induced cytokines and prevented a cytokine storm by targeting IRF-5.

[70]

miR-29c/ Up

IAV

In vitro (A549)

-

Inhibition of inflammation

IAV upregulated miR-29c thus inhibiting the expression of antiviral & proinflammatory genes by targeting A20 mRNA.

[59]

miR-125a and -b

IAV

Human (primary bronchial epithelial cells), In vivo (mice)

MAVS, A20

Induction of inflammation

Overexpression of miR-125a/b increased proinflammatory cytokines by downregulating A20. Downregulation of miR-125a/b increased MAVS expression and anti-IAV responses.

[71]

let-7/-

SARS-CoV-2

In vitro (HEK293T)

SARS-CoV-2 S and M proteins.

Inhibition of inflammation

let-7 inhibited SARS-CoV-2 replication & inflammatory cytokine expression.

[72]

miRNA-223/ Up

SARS-CoV-2

In vivo (mice)

-

Inhibition of inflammation

Pro-inflammatory mediators NLRP3, CXCL2, and IL-6 were upregulated after miRNA-223-3p was inhibited in mice lungs.

[73]

miR-140-5p/ Down

RSV

Human (PBMC, nasal mucosal), In vitro (BEAS-2B)

TLR4

Inhibition of inflammation

TNFα, IL-1β, -6, -8, and overexpression of miR-140-5p have been all reduced. The IFNα-mediated downregulation of TNFα, IL-1β, IL-6, and IL-8 has been decreased by inhibition of miR-140-5p. Downregulation of miR-140-5p promoted RSV replication by targeting TLR4.

[74]

miR-146a/ -

RSV

In vitro (A549 & HEp-2), In vivo (mice)

TRAF-6

Inhibition of inflammation

Ectopic expression of miR-146a suppressed RSV infection as well as reduced inflammatory cytokines by targeting TRAF-6

[75]

miR-146a, miR-146b/

Up

RV

In vitro (pHBEC), In vivo (mice)

-

Inhibition of inflammation

miR-146a/b was significantly downregulated in RSV infection.

miR-146a/b can promote expression of IFN response genes and suppress pro-inflammatory cytokines in HBECs and mouse airways during RSV infection.

[76]

miR-328-3p/ Up

HBV

In vitro (THLE-2), in vivo (mice)

FOXO4

Induction of inflammation

HBV upregulated the expression of miR-328-3p via inducing the binding of STAT3 to its promoter in THLE-2 cells. miR-328-3p inhibited apoptosis, promoted proliferation as well as induced expression of pro-inflammatory cytokines by targeting FOXO4.

[77]

miR-130a/ Down

asymptomatic HBV carriers

In vitro (HepG2), In vivo (mice)

PGC1α and PPARγ

Induction of inflammation

miR-130a decreased HBV replication and activated NF-κB by targeting PGC1α and PPARγ. HBV attenuated inflammation and promoted immune tolerance by decreasing miR-130a and NF-κB activation in asymptomatic HBV carriers.

[78]

miR-146a/ Up

HBV

Human (liver tissue), in vivo (mice)

CFH

Induction of inflammation

HBV increased the expression of miR-146a via inducing NF-κB binding to miR-146a promoter. miR-146a promoted HBV-related liver inflammation by targeting CFH.

[79]

miR-203a/ Up

HBV

In vitro (HepG2)

Rap1a

Induction of inflammation

HBV-HBx protein significantly raised the expression of miR-203a. miR-203a induced hepatic inflammation by targeting Rap1a.

[80]

miR-106a/ Down

Chronic HBV

Human (PBMC)

IL-8

Inhibition of inflammation

miR-106a might have a substantial part in chronic HBV-inflammation by targeting IL-8.

[81]

miR-125a/

Up

HCV

In vitro (huh7)

TRAF6 & MAVS

-

HCV induced expression of miR-125a, and miR-125a promoted HCV replication.

miR-125a modulated IFN signaling by targeting MAVS and TRAF6.

[82]

miRNA-449a and miRNA-107/ Down

HCV

Human (liver tissue), In vitro (primary human hepatocytes & HEPG2)

IL-6R & JAK1

Inhibition of inflammation

HCV promoted CCL2 expression, inflammatory responses and fibrosis via activating the IL-6-mediated signaling cascade by downregulating miR-449a and miR-107 levels.

[83]

miRNA-34a/ Up

HIV-Tat protein

In vitro (BV-2),

In vivo (mice)

NLRC5

Induction of inflammation

By targeting NLRC5, HIV-1 Tat enhanced the production of miR-34a, which in turn caused the proinflammatory cytokines IL-1β and IL-6 to be upregulated in microglia.

[84]

miR-32/ Up

HIV-1 (Tat C)

In vitro (CHME3)

TRAF3

Induction of inflammation

HIV-1 Tat C raised expression of miR-32 and the expression of inflammatory genes in microglial cells by targeting TRAF3.

[85]

miR-126-5p/ Up

chronic HIV-1 infection

Human (primary monocytes)

CYLD

Induction of inflammation

miR-126-5p substantially reduced CYLD during chronic HIV-1 infection, thus promoting monocyte inflammation by inducing pJNK2.

[86]

miR-21/ Down

HIV

Human (monocytes)

IP-10

Inhibition of inflammation

miR-21 inhibited inflammation mediated by monocytes in HIV-infected patients by targeting IP-10.

[87]

miR-146a/

HIV

In vitro (primary human fetal microglial cells, U937)

CCL8/MCP-2

Inhibition of inflammation

HIV increased expression of mir-146a, and inhibited the expression of the proinflammatory chemokine MCP-2. The brain’s HIV-mediated chronic inflammation was maintained in part by mir-146a.

[88]

miR-155/ Up

JEV

In vitro (CHME3), In vivo (BALB/c mice)

PELI1

Inhibition of inflammation

Through the upregulation of miR-155 in human microglial cells, JEV can inhibit the non-canonical NF-κB pathway and pro-inflammatory cytokines (TNF-α and IL-6).

[89]

miR-466d-3p/ Down

JEV (strain P3)

In vitro (mouse neuroblastoma cells)

IL-1β

Inhibition of inflammation

JEV NS3 protein contributed to the degradation of miR-466d-3p within neurons.

Suppression of miR-466d-3p promoted JEV replication and induced IL-1β secretion.

[90]

miR-146a/ Up

JEV

In vitro (C8-B4)

-

Inhibition of inflammation

JEV promoted miR-146a and pro-inflammatory cytokines expressions in mouse brain. miR-146a negatively regulated pro-inflammatory cytokines, through a negative feedback loop in a JEV replication independent fashion.

[91]

miR-15b/ Up

JEV

In vitro (U251 & BV2), In vivo (mouse brain)

RNF125

Induction of inflammation

miR-15b promoted proinflammatory cytokines and interferon type 1 by inhibiting RNF125.

[92]

miR-432/ Down

JEV

In vitro (CHME3)

SOCS5

Induction of inflammation

The upregulation of miR-432 resulted in a rise in pro-inflammatory cytokines, specifically TNF-α and IL-6. JEV may use miR-432 downregulation to avoid host antiviral immune responses.

[75]

miR-19b-3p

JEV

In vitro (U251 & BV2), in vivo (BALB/c mice)

RNF11

Induction of inflammation

miR-19b-3p increased inflammatory cytokines by targeting ring finger protein 11 (RNF11).

[93]

miR-155/ Up

JEV

In vitro (BV-2, primary microglia cells), In vivo (BALB/c mice)

SHIP1

Induction of inflammation

miR-155 induced inflammation by regulating the NF-κB pathway by targeting SHIP1 during JEV infection.

[94]

miR-301a/ Up

JEV

In vitro (CHME3 & BV2), In vivo (BALB/c mice)

NKRF

Induction of inflammation

JEV increased the expression of miR-301a and induced an inflammatory response via targeting NKRF and promoting virus-induced neuroinflammation.

[95]

miR-15/ Up

CVB3

In vitro (H9c2)

NLRX1

Induction of inflammation

Suppression of miR-15 promoted cell viability, reduced apoptosis, myocardiocyte injury, and the inflammatory responses induced by CVB3 infection by modulation of the NLRX1-mediated NLRP3 inflammasomes.

[96]

miR-425-3p/ Down

CVB3

In vivo (mouse myocardial tissue)

TGF-β1

Induction of inflammation

miR-425-3p has been downregulated in Coxsackievirus type B3-infected mice. Upregulation of miR-425-3p led to myocardial inflammation by inhibiting the TGF-β1/smad axis in Coxsackievirus type B3-infected mice.

[97]

miR-221/-222

CVB3 (Viral myocarditis)

In vitro,

in vivo (mice)

CXCL12 & ICAM1

Inhibition of inflammation

The cardiac viral load was markedly elevated by downregulation of miR-221/-222, aggravating heart damage and inflammation.

[98]

miR-302/ Down

Enterovirus 71

Human (PBMC), In vitro (HEK293T & RD)

KPNA2

Inhibition of inflammation

miR-305 significantly downregulated IL-6, TNF-α, and CCL3 in EV71-infected cells by targeting KPNA2. EV71 increased cytokines levels by stimulating KPNA2 expression by inhibition of miR-302 expression.

[99]

miR-124/ Up

Enterovirus 71

In vitro (human rhabdomyosarcoma)

IL-6R, STAT3

Inhibition of inflammation

miR-124 promoted EV71 replication by attenuating the antiviral activity mediated by IL-6R and STAT3.

[100]

miR-206/ Down

Enterovirus 71

In vitro (U-251)

CCL2

Inhibition of inflammation

Overexpression of miR-206 affected severe HEV71 encephalitis by downregulation of CCL2.

[101]

miR-146a/ Up

Dengue virus

In vitro (A549)

TRAF6

Induction of inflammation

By targeting TRAF6, miR-146a boosted TNF-α and IL-6 in A549 cells infected with DENV2. The miR-146a-autophagy axis significantly regulated pro-inflammatory cytokines during dengue virus infection.

[102]

miR-146a/ Up

BoDV1

In vitro (HMC3), In vivo (rats)

IRAK1 and TRAF6

Inhibition of inflammation

miR-146a was significantly upregulated in BoDV-1 infected microglial cells (HMC3). miR-146a contributed to BoDV-1 survival in microglial cells via inhibiting the IRAK1/TRAF6/NF-κB signaling pathway.

[103]

miR-155/ -

West Nile virus

In vitro (SK-N-SH), In vivo (miR-155 knockout mice)

-

Induction of inflammation

miR-155 ameliorated lethal West Nile virus infection by promoting anti-viral cytokines and chemokines.

[104]

miR-221/ Up

HCMV

In Vitro (neural precursor cells)

SOCS1

Inhibition of inflammation

HCMV infection decreased SOCS1 protein by upregulating miR-221 expression, thus suppressing inflammation.

[105]

miR-21/

HSV

In vivo (mice)

-

Induction of inflammation

Downregulation of miR-21 improved HSV-induced Behçet’s Disease (BD)-like inflammatory symptoms as well as decreased pro-inflammatory cytokines IL-17 as well as IL-6.

[106]

miR-146a/ Up

CHIKV

In vitro (primary human synovial fibroblasts)

TRAF6, IRAK1, IRAK2

Inhibition of inflammation

MiR-146a inhibition reduced CHIKV replication. Overexpression of miR-146a reduced inflammatory cytokines (TNF-, IL-1, and IL-6), and promoted CHIKV replication.

[107]

miR-146a/

Up

ZIKV/ NS1

In vitro (HMC3)

STAT-1 & TRAF6

Inhibition of inflammation

miR-146a downregulated STAT-1 & TRAF6 and led to inhibition of pNF-κBp65 & TNF-α.

ZIKV-NS1 suppressed pro-inflammatory & antiviral responses by increasing miR-146a expression in human microglial cells.

[108]

miR-21-5p/

Up

CHPV

In vitro (CHME3)

PTEN

Induction of inflammation

The expression of miR-21-5p was significantly increased in CHPV‑infected CHME3 cells. miR-21-5p induced NF-ĸB activity and pro-inflammatory responses throughout CHPV infection.

[109]

EBV-miR-BART11/ Up

EBV

In vitro (MKN-45, SGC-7901, THP-1)

FOXP1

Induction of inflammation

Upregulation of EBV-miR-BART11 level induced gastric cancer cell progression and metastasis mediated by inflammation.

[110]

HSV-1 miR-H6

HSV-1

In vitro (HCE)

HSV-1-ICP4

Inhibition of inflammation

In vitro, HSV-1 miR-H6 decreased IL-6 expression and HSV-1 multiplication in human corneal epithelial cells.

[111]

KSHV miRNAs (miR-K12-1, − 3, −7, − 9, and − 11)

KSHV

In vitro (BCBL-1)

-

Induction of inflammation

KSHV miRNAs induced IL-6 along with IL-10 expression in macrophages by down-regulating C/EBPβ.

[112]