Background: Influenza A virus (IAV) greatly affects public health in recent decades. Accumulating data indicated that host microRNAs (miRNAs) were related to IAV replication. This 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 RNA immunoprecipitation (RIP) assay were used to verify the interaction between miR-21-3p and FGF2.</p>  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.