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.

Pathogenicity of duck plague and innate immune responses of the Cherry Valley ducks to duck plague virus

“…In one study, Wei et al . showed the mRNA expression of MDA5 was up-regulated by 46 fold in the spleen of Muscovy ducks following-highly pathogenic avian influenza H5N1 infection30. Since PRRs were activated other than MDA5, it is not surprising that IPS-1, an adaptor protein of RLRs pathway, upregulated in the spleen and brain, the immune response through the MDA5 pathway may not play a decisive role.…”

Dietary Administration of Bacillus subtilis Enhances Growth Performance, Immune Response and Disease Resistance in Cherry Valley Ducks

“…The activation of duRIG-I signaling induces the expression of downstream innate immune genes including Mx, PKR , and IFN -β (Barber et al, 2013). Since MDA5 is a strong inducer of antiviral molecules and pro-inflammatory cytokines such as IL-2, IL-6, IFN -α, and IFN -γ (Wei et al, 2014), the upregulation of cytokines and antiviral proteins expression might have stemmed from the activation of these receptors.…”

Molecular cloning, characterization and mRNA expression of duck interleukin-17F

“…Expression levels of duIL-17A and duIL-17F were determined using the following primers: duIL-17A; forward 5 -ATGTCTCCAACCCTTCGT-3 , reverse 5 -CCGTATCACCTTCCCGTA-3 and duIL-17F; forward 5 -CTGAGAGACTTAATGGAGACTG-3 , reverse 5 -AGAATCTGAACGGCTGATG-3 . IFN-␣, IL-1␤, IL-6, IL-8 primers (Wei et al, 2014a) were used to evaluate the biological activity of duIL-17F and duIL-17A. Real-time RT-PCR was performed in duplicate using a CFX96 real-time PCR system (Bio-Rad, USA).…”