Avian infectious bronchitis virus disrupts the melanoma differentiation associated gene 5 (MDA5) signaling pathway by cleavage of the adaptor protein MAVS

Yu, Liping; Zhang, Xiaorong; Wu, Tianqi; Su, Jin; Wang, Yuyang; Wang, Yuexin; Ruan, Baoyang; Niu, Xiaosai; Wu, Yantao

Infectious bronchitis (IB) is a serious and highly contagious disease in chickens that is caused by the infectious bronchitis virus (IBV) [1] . Although the host uses multiple mechanisms to thwart viral invasion, the overall clearance and outcome of IBV infection in chickens are critically dependent on the early protection provided by the innate immune system [2] . To enable its survival, IBV has evolved to disrupt the activation of the host antiviral signaling pathway using a number of mechanisms, such as delaying the activation of the IFN response during the early stages of IBV infection [3, 4] . The innate immune system plays a critical role in the detection and elimination of invading pathogens, especially the IFN antiviral immune response [5] . To activate the antiviral immune response, pattern recognition receptors (PRRs) recognize specific pathogenassociated molecular patterns (PAMPs) [6, 7] . The PRRs include Toll-like receptors (TLRs), retinoic acidinducible gene I (RIG-I)-like receptors (RLRs), and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs). RLRs include RIG-I [8] , melanoma differentiation associated gene 5 (MDA5) [9] and laboratory of genetics and physiology 2 (LGP2) [10] . RIG-I and MDA5 interact with the mitochondrial antiviral signaling gene (MAVS, also called IPS-1/VISA/CARDIF) [11] , a critical downstream adaptor protein located at the mitochondrial membrane, via caspase activation and recruitment domains (CARD)-CARD domains at their N-terminal [12] . Activated MAVS can recruit downstream interferon regulatory factor-3/7 (IRF3/IRF7) and the transcriptional factor nuclear factor κB (NF-κB) [13] , leading to the rapid production of type I IFNs and proinflammatory cytokines [11, 14, 15] .