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 diseases are a manifestation of constant battles between the host and pathogenic microbes. This host-pathogen antagonism is demonstrated by the interaction between viruses and MAVS, a critical molecule that is downstream of MDA5 and RIG-I [11, 41] . For example, MAVS can orchestrate a strong immune response against hepatitis C virus (HCV), but HCV counterattacks by cleaving MAVS, thus crippling the immune response [42, 43] . MAVS activity was proposed to be linked to both peroxisomes and mitochondrial location in the assembly of a macromolecular signaling complex [13] . When MAVS was cleaved and released to the outside of mitochondria, such as the endoplasmic reticulum or cytoplasm, it failed to signal [13, 44] . IBV can efficiently cleave MAVS in the early stages of infection, leading to the blockage of IFN expression. Furthermore, chIFN-β expression, induced by IBV infection, was effectively inhibited by blocking the expression of MAVS using siRNA. More significant results were observed when MAVS was silenced together with siMDA5. In conclusion, we showed that chMAVS acts as a key modulator of antiviral signaling by regulating chMDA5-mediated signaling in IBV-infected cells. Future studies should focus on more detailed aspects of host-pathogen interactions that involve chMAVS to gain control of the host immune system.