Duck viral enteritis (DEV) is a DNA virus that leads to heavy economic losses in the commercial duck industry. As a key cytoplasmic sensor, melanoma differentiation-associated gene 5 (MDA5) can recognize viral RNA and enhance the antiviral immune response. Retinoic acid-inducible gene-I (RIG-I) and MDA5 both belong to the RIG-I-like receptors family, and RIG-I is known to be involved in the anti-DEV signaling pathway. However, the role of MDA5 in DEV infection remains unclear. In this study, we used overexpression and knockdown methods to determine if MDA5 affected DEV infection in ducks. We confirmed that DEV infection was significantly suppressed in MDA5-overexpressing DEF cells, while knockdown of MDA5 by si... More
Duck viral enteritis (DEV) is a DNA virus that leads to heavy economic losses in the commercial duck industry. As a key cytoplasmic sensor, melanoma differentiation-associated gene 5 (MDA5) can recognize viral RNA and enhance the antiviral immune response. Retinoic acid-inducible gene-I (RIG-I) and MDA5 both belong to the RIG-I-like receptors family, and RIG-I is known to be involved in the anti-DEV signaling pathway. However, the role of MDA5 in DEV infection remains unclear. In this study, we used overexpression and knockdown methods to determine if MDA5 affected DEV infection in ducks. We confirmed that DEV infection was significantly suppressed in MDA5-overexpressing DEF cells, while knockdown of MDA5 by siRNA markedly enhanced DEV growth. We demonstrated that overexpression of duck MDA5 significantly upregulated expression of interferon (IFN)-stimulated genes, including myxovirus resistance protein (Mx), IFN-induced oligodenylate synthetase-like (OASL), IFN-induced transmembrane protein 1 (IFITM1) and IFN-β. In addition, the transcriptional level of MDA5 was upregulated both in vivo and in vitro upon DEV infection. We also showed that there was an association between MDA5 and laboratory of genetics and physiology 2 (LGP2) in antiviral signaling. LGP2 functioned as a concentration-dependent switch between MDA5-specific enhancement and interference. Overall, these findings indicated that MDA5 restricted DEV replication and LGP2 plays a critical role in MDA5-mediated antiviral activity against DEV.,Copyright © 2019 Elsevier Ltd. All rights reserved.
