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

Although chMDA5 was found to be capable of sensing IBV, leading to the induction of chIFN-β expression in chicken cells, the overexpression of chIFN-β induced by chMDA5 and dgRIG-I did not affect the viral replication in our experiment. Silencing of chMDA5 also had little impact on IBV replication, and a subtle role for chMDA5 may be masked by incomplete silencing of chMDA5, resulting in trace levels of IFN activity. Nevertheless, our data gave a similar result as mammalian models showing that MDA5 is not critical to combat the influenza virus [23] . It is known that type I IFNs are induced by the infection of host cells with viruses and that secreted type I IFNs cause cells to express various antiviral proteins, such as myxovirus-resistance protein (Mx) GTPase, ribonuclease L (RNase L), RNAdependent protein kinase (PKR), oligoadenylate synthetase (OAS), and interferon stimulated gene (ISG) by autocrine and paracrine mechanisms [27] . Previous studies have suggested that IBV replication was reduced by 50%, as measured by syncytia formation, after a treatment with 100 U/ml of IFN [39, 40] . This implies that even in cells responding to type I IFN, the autocrine and paracrine effects of IFNs from virus-infected cells may not be sufficient to suppress viral replication. IBV delays the IFN response at an early stage of infection in chicken cells, since it needs time to infect neighboring cells before the establishment of an antiviral state induced by IFN [25] , which is secreted paracrinely by chMDA5 and dgRIG-I mediated induction in IBV-infected cells. The data in Fig. 4 also support this conclusion, which suggests that the expression level of IFN in the group infected with a higher dose of IBV was higher than in the group that received a lower dose.