Porcine haemagglutinating encephalomyelitis virus deactivates transcription factor IRF3 and limits type I interferon production.

Li, Zi; Yang, Yawen; Lu, Huijun; Zhang, Jing; Xu, Rongyi; Shi, Junchao; Lan, Yungang; Guan, Jiyu; Zhao, Kui; He, Hongbin; Gao, Feng; He, Wenqi

Porcine haemagglutinating encephalomyelitis virus (PHEV) is a member of coronavirus that causes acute infectious disease and high mortality in piglets. The transcription factor IRF3 is a central regulator of type I interferon (IFN) innate immune signalling. Here, we report that PHEV infection of RAW264.7 cells results in strong suppression of IFN-β production in the early stage. A comparative analysis of the upstream effector of IFN-β transcription demonstrated that deactivation of IRF3, but not p65 or ATF-2 proteins, is uniquely attributed to failure of early IFN-β induction. Moreover, the RIG-I/MDA5/MAVS/TBK1-dependent protective response that regulates the IRF3 pathway is not disrupted by PHEV and works well underlying the deactivated IRF3-mediated IFN-β inhibition. After challenge with poly(I:C), a synthetic analogue of dsRNA used to stimulate IFN-β secretion in the TLR-controlled pathway, we show that PHEV and poly(I:C) regulate IFN-β-induction via two different pathways. Collectively, our findings reveal that deactivation of IRF3 is a specific mechanism that contributes to termination of type I IFN signalling during early infection with PHEV independent of the conserved RIG-I/MAVS/MDA5/TBK1-mediated innate immune response.