Rhabdovirus-Inducible MicroRNA-210 Modulates Antiviral Innate Immune Response via Targeting STING/MITA in Fish

Abstract

Viral infection induces type I IFN production, which plays critical roles in orchestrating the antiviral defense by inducing direct antiviral activities. To establish a persistent infection, viruses have evolved numerous strategies to specifically interfere with IFN production or its downstream mediators, thereby evading the immune responses. MicroRNAs (miRNAs) are a family of small noncoding RNAs that posttranscriptionally regulate the expressions of specific target genes. Although accumulating evidence demonstrates that miRNAs play vital roles in regulating viral infection, miRNAs that target intracellular sensors and adaptors of innate immunity have not been fully uncovered. In this paper, we identify fish miR-210 as a robust regulator involved in regulating virus-host interactions. We found that rhabdovirus significantly upregulated the expression of fish miR-210. Inducible miR-210 modulates virus-triggered type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING), thereby promoting viral replication. Furthermore, we demonstrated that miR-210 regulates innate immune response through NF-κB, IFN regulatory factor 3, and JAK/STAT signaling pathways. The collective findings indicate that inducible miR-210 plays a regulatory role in virus-host interactions through STING-mediated singling pathway by targeting STING.

Non-coding RNAs Function as Immune Regulators in Teleost Fish

“…The upregulation of miR-210 could indirectly induce the RIG-I signaling pathway and enhanced the expression of type I IFN by targeting deubiquitinating enzyme A (DUBA), thus protecting the host from viral infection. Likewise, miR-210 was found to be upregulated in Siniperca chuatsi rhabdovirus (SCRV)-infected miiuy croaker ( 60 ). However, further study indicated that miR-210 inhibited type I IFN and inflammatory cytokine production by targeting stimulator of IFN genes (STING) and repressing NF-κB, IRF3 and IFN-stimulated response element (ISRE) signaling.…”

MicroRNA‐92a inhibits macrophage antiviral response by targeting retinoic acid inducible gene‐I

“…miR‐30c can be induced by porcine reproductive and respiratory syndrome virus and serves as a suppressor of IFN‐I signaling by targeting JAK1 . Rhabdovirus inhibits antiviral immunity by upregulating the miR‐210, which targets stimulator of IFN genes and dampens IRF3 signaling . Our study identifies miR‐92 as a new member of the virus‐induced microRNA category that disrupts host antiviral signaling.…”

MicroRNA regulation of Toll‐like receptor, RIG‐I‐like receptor and Nod‐like receptor pathways in teleost fish

“…Researchers found that inducible miR‐210 could modulate virus‐triggered type I IFN and inflammatory cytokine production through NF‐κB, IFN regulatory factor 3 (IRF3) and JAK/STAT signalling pathways, thereby promoting viral replication. Further investigations confirmed that miR‐210 has a similar regulatory role in some other fish species, such as Sciaenops ocellatus and Larimichthys crocea , indicating its evolutionary conservation and functional consistency in teleost (Xu et al 2018a). In Japanese flounder, previous studies have identified a large amount of miRNAs and indicated many of these flounder miRNAs potentially target key genes in immune responses.…”

“…Until now, most studies on fish miRNAs have applied bioinformatics prediction methods to suggest target genes, whereas only a few studies have carried out validation of target genes using experimental methods (Zhang et al 2014a, 2016, 2017; Cui et al 2016, 2017; Wang et al 2016c; Xu et al 2016c, 2018a, 2018b, 2018c, 2018d; Bi et al 2017; Han et al 2017, 2018; Chu et al 2017a, 2017b, 2017c, 2017d; Ni et al 2018; Sun et al 2018). Furthermore, fewer studies have examined how miRNAs regulate target genes and their effects on signalling pathways (Cui et al 2016, 2017; Zhang et al 2016; Wang et al 2016c; Xu et al 2016c, 2018a, 2018b, 2018d; Bi et al 2017; Han et al 2017, 2018; Chu et al 2017a, 2017b, 2017d; Ni et al 2018; Sun et al 2018). Therefore, on the basis of a large number of preliminary investigations using high‐throughput sequencing, it is urgently necessary to carry out function validations on miRNA, including researches on target gene verification and regulation mechanisms.…”