MicroRNA-21-3p modulates FGF2 to facilitate influenza A virus H5N1 replication by refraining type I interferon response

Abstract

Background: Influenza A virus (IAV) has greatly affected public health in recent decades. Accumulating data indicated that host microRNAs (miRNAs) were related to IAV replication. The present study mainly focused on the effects of microRNA-21-3p (miR-21-3p) on H5N1 replication. Methods: The levels of miR-21-3p, virus structural factors (matrix 1 (M1), nucleoprotein (NP)), type I interferon (IFN) response markers (IFN-β, IFN-α), IFN-stimulated genes (protein kinase R (PKR), myxovirus resistance A (MxA), 2′-5′-oligoadenylate synthetase 2 (OAS)), and fibroblast growth factor 2 (FGF2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of M1, NP, and FGF2 were tested by Western blot assay. The virus titer was assessed by tissue culture infective dose 50% (TCID50) assay. The dual-luciferase reporter assay and ribonucleic acid (RNA) immunoprecipitation (RIP) assay were used to verify the interaction between miR-21-3p and FGF2. Results: MiR-21-3p was reduced in H5N1-infected patients and A549 cells. MiR-21-3p overexpression facilitated the levels of M1, NP, TCID50 value, and reduced the levels of IFN-β, IFN-α, PKR, MxA, and OAS in H5N1-infected A549 cells. FGF2 was verified as a direct target of miR-21-3p. The introduction of FGF2 counteracted miR-21-3p-mediated decrease in the levels of M1, NP, and TCID50 value, as well as reduction in the levels of IFN-β, IFN-α, PKR, MxA, and OAS in H5N1-infected A549 cells. Conclusion: MiR-21-3p down-regulated FGF2 expression to accelerate H5N1 replication and confine IFN response.

Downregulation of microRNA‑221 facilitates H1N1 influenza A virus replication through suppression of type‑IFN response by targeting the SOCS1/NF‑κB pathway

“…Zhang et al ( 40 ) showed that miR-146a was significantly upregulated during IAV infection and miR-146a downregulation led to a significant reduction in IAV replication by enhancing the type-I IFN response. Shi et al ( 41 ) found that miR-21-3p downregulated fibroblast growth factor 2 expression to accelerate IAV replication by impairing the IFN response. The current study demonstrated that IAV infection modulated the expression profile of miRNA in host cells.…”

MiR-4334-5p Facilitates Foot and Mouth Disease Virus Propagation by Suppressing Interferon Pathways via Direct Targeting ID1

“…Emerging evidences indicate that the host microRNAs (miRNAs) have a significant effect on the comprehensive host-pathogen interaction [ 7 ], even participating in the viral life cycle. For instance, miR-101 represses feline herpesvirus 1 reproduction by targeting cellular suppressor of cytokine signaling 5 to promote IFN-I signaling [ 20 ]; miR-7 suppresses rotavirus replication via targeting viral NSP5 directly [ 21 ]; miR-122 reduces HBV gene expression and replication via binding with hepatitis B virus pre-genomic RNA sequence [ 22 ]; miR-21-3p promotes influenza A virus H5N1 replication by regulating FGF2 to repress IFN-I signaling [ 23 ]; miR-545 promotes enterovirus 71 propagation through directly targeting phosphatase and tensin homolog and tumor necrosis factor receptor-associated factor 6 [ 24 ]. In the case of FMDV, there are only a few studies, artificial miRNA targeting 3D polymerase is efficient to inhibit FMDV replication [ 25 ], miR-1307 and miR-203a repress FMDV infection [ 2 , 15 ].…”

The Importance of miRNA Identification During Respiratory Viral Infections

“…Some respiratory viruses have been reported to induce miRNAs implicated in viral replication and immune response modulation [22]. Some examples include influenza A virus (IAV) [7,7,[23][24][25][26][27][28], human respiratory syncytial virus (HRSV) [15,[29][30][31][32][33][34], human metapneumovirus (HMPV) [15,21], adenovirus (ADV) [35], and due to the global health crisis miRNAs have been studied recently in SARS-CoV-2 infection [36].…”

“…On the other hand, IAV H5N1 diminishes levels of miR-21–3p in infected patients and A549 cells. miR-21–3p, downregulates IFN response (IFN-β, IFN-α, PKR, MxA, and OAS) by targeting the regulating fibroblast growth factor 2 (FGF2) [ 28 ]. It has also been shown that IAV H5N1 downregulates the miRNA family (30-a, -b, -c, -d, and -e) in cell lines.…”