Seneca valley virus antagonises host antiviral response by activating autophagy to degrade FBXW7

Abstract:

[Background] Seneca valley virus (SVV) can cause severe blistering in pigs. Due to the lack of commercial vaccines, it is essential to probe into the interactions of SVV with host antiviral molecules. [Objective] To investigate the role of the E3 ubiquitin ligase, F-box and WD repeat domain containing 7 (FBXW7), in anti-SVV infection. [Methods] The small interfering RNA (siRNA) was employed to knock down FBXW7. RT-qPCR, TCID₅₀, and Western blotting were employed analyze the effect of FBXW7 on SVV replication and cytokines in PK-15 cells. [Results] Western blotting results showed that SVV infection down-regulated the expression of FBXW7 in PK-15 cells. The knockdown of FBXW7 promoted SVV replication and down-regulated the mRNA levels of interleukin-6 (IL-6), interferon-β (IFN-β), and tumor necrosis factor-α (TNF-α). When ATG5 was knocked down to inhibit autophagy, FBXW7 protein degradation was inhibited and SVV replication decreased. [Conclusion] FBXW7 has an inhibitory effect on the replication of SVV which mediates FBXW7 degradation by activating autophagy. The finding provides a new strategy for the development of antiviral targets.