title: Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections.
abstract: Melanoma differentiation-associated gene 5 (MDA5) is an important intracellular receptor that recognizes long molecules of viral double-stranded RNA in innate immunity. To understand the mechanism of duck MDA5-mediated innate immunity, we cloned the MDA5 cDNA from the Muscovy duck (Cairina moschata). Quantitative real-time PCR analysis indicates that duck MDA5 mRNA was constitutively expressed in all sampled tissues. A significant increase of MDA5 mRNA was detected in the brain, spleen and lungs of ducks after infection with an H5N1 highly pathogenic avian influenza virus (HPAIV). We investigated the role of the predicted functional domains of MDA5. The results indicate the caspase activation and recruitment domain (CARD) of duck MDA5 had a signal transmission function through IRF-7-dependent signaling pathway. Overexpression of the CARD strongly activated the chicken IFN-β promoter and upregulated the mRNA expression of antiviral molecules (such as OAS, PKR and Mx), proinflammatory cytokines (such as IL-2, IL-6, IFN-α and IFN-γ, but not IL-1β and IL-8) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) (RIG-I and LGP2) without exogenous stimulation. We also demonstrate the NS1 of the H5N1 HPAIV inhibited the duck MDA5-mediated signaling pathway in vitro. These results suggest that duck MDA5 is an important receptor for inducing antiviral activity in the host immune response of ducks.
authors.forename: Liangmeng
authors.initials: L
authors.lastname: Wei
authors.forename: Jin
authors.initials: J
authors.lastname: Cui
authors.forename: Yafen
authors.initials: Y
authors.lastname: Song
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Fei
authors.initials: F
authors.lastname: Han
authors.forename: Runyu
authors.initials: R
authors.lastname: Yuan
authors.forename: Lang
authors.initials: L
authors.lastname: Gong
authors.affiliation: College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. prjiao@scau.edu.cn.
authors.forename: Peirong
authors.initials: P
authors.lastname: Jiao
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004372:Ducks; D005347:Fibroblasts / Q000502:physiology / Q000821:virology; D007113:Immunity, Innate; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000235:genetics / Q000276:immunology* / Q000821:virology; D008969:Molecular Sequence Data; D011201:Poultry Diseases / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016415:Sequence Alignment / Q000662:veterinary; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D030161:Avian Proteins; D018076:DNA, Complementary; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins