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          that were involved in major antiviral pathways were differen-  inhibitor (SSI) protein family, contains eight members including
          tially expressed as analysed by KEGG and GO pathway analysis   SOCS1–7 and CIS protein. The SOCS proteins are key negative
          database (Fu et al., 2018a). Among them, 214 chicken miRNAs   regulators of cytokine and growth factor signalling. Targeting of
          (gga-miRNAs) were engaged in JAK-STAT signalling pathway,   SOCS5 by gga-miR-130b inhibits SOCS5 expression, which,
          207  gga-miRNAs  in  Toll-like  receptor mediated  signalling   in turn, enhances the mRNA expressions of STATs. As STATs
          pathway, 164 gga-miRNAs in RLR (MDA5) receptor mediated   are involved in type I interferon expression that plays a major
          signalling  pathway  and  244  gga-miRNAs  in cytokine-cytokine   role in host antiviral response. Thus, the enhancement of STAT
          receptor signalling pathway, suggesting that gga-miRNAs are   expression by gga-miR-130b-mediated suppression of SOCS5
          involved in cell response to IBDV infection. As shown in Fig. 7.4,   contributes to the inhibition of IBDV replication. Likewise, gga-
          gga-miR-130b inhibits IBDV replication via targeting the spe-  miR-454 suppresses IBDV replication via directly targeting IBDV
          cific sequence of IBDV segment A and enhances the expression   genomic segment B and cellular SOCS6 (Fu et al., 2018b), and
          of IFN-β by targeting Suppressors of Cytokine Signalling 5   gga-miR-155 enhances IFN-β expression and suppresses IBDV
          (SOCS5) in host cells (Fu et al., 2018a). SOCS5 is a member of   replication via targeting SOCS1 and TANK (Wang et al., 2018b),
          SOCS family. This family, also known as STAT-induced STAT   suggesting  that  miRNAs  inhibit  IBDV  replication  via  directly




















































          Figure 7.4  Schematic illustration of the roles of chicken microRNAs in host response to IBDV infection. The biogenesis of miRNAs involves
          multiple steps as briefly described in the text. The functional miRNA strand is then selectively loaded onto Argonaute protein and forms
          RISC along with other proteins such as GW182. Mature miRNAs then guide the RISC to cognate target genes for mRNA degradation or
          translational repression. Upon IBDV infection, chicken cell expresses miRNAs (miR-155, miRNA-130b, miR-454 and so on) that target the
          transcript(s) of host SOCS1, 5 and 6 and TANK, negative regulators of immune response, to enhance interferon expressions, leading to the
          inhibition of IBDV replication. Furthermore, chicken miRNA-130b and miR-454 directly target viral RNA of IBDV, inhibiting viral replication.
          On the contrary, chicken miR-9*, miR-2127 and miR-142-5p target the mRNAs of IRF2, P53 and MDA5, respectively, positive regulators of
          immune response and a pattern recognition receptor, to inhibit host innate defence and favour viral replication. Abbreviations: gg-miRNA,
          chicken microRNA; IRF, interferon regulatory factor; MDA5, melanoma differentiation-associated gene 5; miRNA or miR, microRNA; SOCS
          Suppressor of cytokine signalling; STAT, signal transducer and activator of transcription; TANK, TRAF family member associated NF-κB
          activator.
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