MicroRNA gga-miR-130b Suppresses Infectious Bursal Disease Virus Replication via Targeting of the Viral Genome and Cellular Suppressors of Cytokine Signaling 5

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally through silencing or degrading their targets, thus playing important roles in the immune response. However, the role of miRNAs in the host response against infectious bursal disease virus (IBDV) infection is not clear. In this study, we show that the expression of a series of miRNAs was significantly altered in DF-1 cells after IBDV infection. We found that the miRNA gga-miR-130b inhibited IBDV replication via targeting the specific sequence of IBDV segment A and enhanced the expression of beta interferon (IFN-β) by targeting suppressors of cytokine signaling 5 (SOCS5) in host cells. These findings indicate that gga-miR-130b-3p plays a crucial role in host defense against IBDV infection. This work shows that gga-miR-130b suppresses IBDV replication via directly targeting the viral genome and cellular SOCS5, the negative regulator for type I interferon expression, revealing the mechanism underlying gga-miR-130-induced inhibition of IBDV replication. This information will be helpful for the understanding of how host cells combat pathogenic infection by self-encoded small RNA and furthers our knowledge of the role of microRNAs in the cell response to viral infection.

miR-26a Inhibits Feline Herpesvirus 1 Replication by Targeting SOCS5 and Promoting Type I Interferon Signaling

“…In this study, overexpression of SOCS5 can inhibit IFN-induced signalling and promote FHV-1 replication, while knockdown of endogenous SOCS5 enhances the IFN-I signalling cascade and suppresses FHV-1 replication (Figure 7), which further verified the negative regulatory role of SOCS5. Previous studies have reported that some miRNAs are involved in the innate immune response by targeting SOCS family proteins [22][23][24]. We found that miR-26a can directly target SOCS5 and decrease its expression and promote the STAT1 phosphorylation, which is used to inhibit viral replication by the host.…”

“…Previous studies have reported that some miRNAs may inhibit virus replication by directly targeting viral genome [23], so, to further elucidate the underlying mechanism of miR-26a attenuating Then, the supernatants were collected for measuring virus titres via the virus plaque assay (A), and cell pellets were used to analyze FHV-1 protein expression (A) by WB or detect viral DNA copies (B) by absolute quantification PCR, respectively. GAPDH was used as an internal control in qPCR, and NC mimics (NC) and NC inhibitors (NC-I) served as negative controls.…”

“…Previous studies have reported that some miRNAs may inhibit virus replication by directly targeting viral genome [23], so, to further elucidate the underlying mechanism of miR-26a attenuating FHV-1 replication, we first analysed miR-26a targets within both FHV-1 sense and antisense RNA sequences using RNA22 (https://cm.jefferson.edu/rna22/Interactive/), but found no potential target sites in FHV-1 RNA. Then, the potential targets of miR-26a in the host were predicted using Targetscan software (http://www.targetscan.org/vert_71/).…”

“…miR-30a-5p downregulated the expression of SOCS1 and SOCS3 via directly targeting their 3' UTRs [22], which also enhanced IFN-I antiviral signalling. miR-130b and miR-432 enhanced the expression of IFN-β by targeting cellular SOCS5 [23,24]. During viral infection, host innate immunity is blocked at an early stage, and our previous studies also suggested that activated type I IFN signalling was quickly suppressed after FHV-1 infection [13], but some miRNAs are still upregulated to enhance IFN signalling pathways [21,23].…”

“…miR-130b and miR-432 enhanced the expression of IFN-β by targeting cellular SOCS5 [23,24]. During viral infection, host innate immunity is blocked at an early stage, and our previous studies also suggested that activated type I IFN signalling was quickly suppressed after FHV-1 infection [13], but some miRNAs are still upregulated to enhance IFN signalling pathways [21,23]. More importantly, it has been reported that some microRNAs can also inhibit virus replication by targeting viral genomes directly [25,26].…”