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

Abstract

BackgroundMelanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection.ResultsHere, we showed that chicken cells transfected with domestic goose RIG-I (dgRIG-I) exhibited increased IFN-β activity after IBV infection. We also found that IBV can cleave MAVS, an adaptor protein downstream of RIG-I and MDA5 that acts as a platform for antiviral innate immunity at an early stage of infection.ConclusionsAlthough chicken MDA5 (chMDA5) is functionally active during IBV infection, the absence of RIG-I may increase the susceptibility of chickens to IBV infection, and IBV may disrupt the activation of the host antiviral response through the cleavage of MAVS.Electronic supplementary materialThe online version of this article (doi: 10.1186/s12917-017-1253-7) contains supplementary material, which is available to authorized users.

Targeted Knockout of MDA5 and TLR3 in the DF-1 Chicken Fibroblast Cell Line Impairs Innate Immune Response Against RNA Ligands

“…A recent study has demonstrated that cSTING acts as a mediator of type I IFN induction through MDA5-STING-IFN-β pathways in response to AIV and Newcastle disease virus (NDV) (67). Furthermore, the knockdown study revealed that cMDA5 is involved in antiviral response to infection of infectious bronchitis virus (IBV) in DF-1 cells (68). It suggests that cMDA5 functions as a sensor of other RNA viruses, such as NDV and IBV.…”

Antiviral responses against chicken respiratory infections: Focus on avian influenza virus and infectious bronchitis virus

“…Activated MAVS can recruit downstream IRF7 and NF-κB, leading to the rapid production of type I IFNs and pro-inflammatory cytokines. The cleavage of MAVS, which occurs at the early stage of the infection, allows IBV to escape MDA5-mediated antiviral responses and to disrupt the activation of the host antiviral response [83].…”

Autophagy induced by avian reovirus enhances viral replication in chickens at the early stage of infection

“…Cells adhering to plates at 37 °C and 5% CO 2 were used for cell culture passage. ARV strain GX/2010/1 was propagated in CEF cells, and the titer was determined as the median tissue culture infective dose (TCID 50 ) as described previously [26]. The complete genomic sequence of the ARV strain GX/2010/1 was deposited in GenBank (accession numbers KJ476699-KJ476708).…”