Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections

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)...

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Bibliographic Details
Published in:Veterinary research (Paris) 2014-06, Vol.45 (1), p.66-66, Article 66
Main Authors: Wei, Liangmeng, Cui, Jin, Song, Yafen, Zhang, Shuo, Han, Fei, Yuan, Runyu, Gong, Lang, Jiao, Peirong, Liao, Ming
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
antiviral properties
Avian Proteins - chemistry
Avian Proteins - genetics
Avian Proteins - metabolism
brain
Cairina moschata
caspases
chickens
Cloning, Molecular
complementary DNA
DNA, Complementary - genetics
DNA, Complementary - metabolism
double-stranded RNA
Ducks
Fibroblasts - physiology
Fibroblasts - virology
gene expression regulation
gene overexpression
Genes
Genetic aspects
Health aspects
immune response
Immunity, Innate
Influenza A virus
Influenza A Virus, H5N1 Subtype - genetics
Influenza A Virus, H5N1 Subtype - immunology
Influenza in Birds - genetics
Influenza in Birds - immunology
Influenza in Birds - virology
innate immunity
interferon-alpha
interferon-beta
interferon-gamma
interleukin-1beta
interleukin-2
interleukin-6
interleukin-8
Life Sciences
lungs
melanoma
messenger RNA
Molecular Sequence Data
Poultry Diseases - genetics
Poultry Diseases - immunology
Poultry Diseases - virology
quantitative polymerase chain reaction
receptors
Sequence Alignment - veterinary
Signal Transduction
spleen
tissues
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
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Summary: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.
ISSN:1297-9716
0928-4249
1297-9716
DOI:10.1186/1297-9716-45-66