Abstract
MDA5 belongs to the RIG-I-like receptor family, which is involved in innate immunity. During viral infection, MDA5 generates an antiviral response by recognizing the ligand to activate interferon. However, the role and mechanism of MDA5 in canine influenza virus (CIV) infection are unclear. To understand the mechanism of canine MDA5-mediated innate immunity during CIV infection, we detected the distribution of MDA5 in beagles, and the structural prediction showed that MDA5 was mainly composed of a CARD domain, RD domain, and DExD/H helix structure. Moreover, we found that MDA5 inhibits CIV replication. Furthermore, in the dual luciferase assay, we revealed that the CARD region of MDA5 strongly activated the IFN-β promoter and mainly transmitted signals through the CARD region. Overexpression of the CARD region of MDA5 revealed that the MDA5-mediated signaling pathway could transmit signals by activating the IRF3/NF-κB and IRF3 promoters, promoting the expression of antiviral proteins and cytokine release, thereby inhibiting CIV replication. Upon silencing of MDA5, cytokine production decreased, while the replication ability of CIV was increased. Thus, this study revealed a novel mechanism by which MDA5 mediated CIV infection and provided new avenues for the development of antiviral strategies.
Highlights
Canine influenza (CI) is a contact respiratory disease caused by the canine influenza virus (CIV), belonging to the Orthomyxovirus type A influenza virus family [1]
The melanoma differentiation associated gene 5 (MDA5) gene was cloned from the spleen of the dog, which consisted of 3089 bp and expressed
The results indicated that after activation of MDA5, the RIG-I pathway and its downstream IFN-stimulated genes (ISGs) were activated by the caspase recruiting domain (CARD) region to induce the production of antiviral proteins, thereby resisting viral invasion
Summary
Canine influenza (CI) is a contact respiratory disease caused by the canine influenza virus (CIV), belonging to the Orthomyxovirus type A influenza virus family [1]. The main epidemic strain of CI is H3N2, but different subtypes have been reported in virus-infected dogs, including H1N1 [4,5], H10N8 [6], avian H9N2 [7], H5N1 [8,9], and avian H9N2 containing the canine influenza PA gene [10]. Dogs are the natural host of CIV, researchers have successfully infected pigs and mice with the CIV [12,13], and researchers isolated equine flu from pig and donkey in China [14,15], which spread across the host due to the high variability of influenza viruses. Further studies of canine innate immune response are important to control the spread of the virus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
