Regulation of MDA5-dependent anti-Tembusu virus innate immune responses by LGP2 in ducks.

Vet Microbiol

College of Animal Science and Veterinary Medicine, Sino-German Cooperative Research Centre for Zoonosis of Animal Origin of Shandong Province, Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Shandong Agricultural University, 61 Daizong Street, Tai'an City, 271018, Shandong Province, China; Collaborative Innovation Center for the Origin and Control of Emerging Infectious Diseases, College of Basic Medical Sciences, Shandong First Medical University, Tai'an City, 271000, Shandong Province, China. Electronic address:

Published: December 2021

Melanoma differentiation associated factor 5 (MDA5), which belongs to the retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) family, has been proved to be a key pattern recognition receptor of innate antiviral signaling in duck, which plays an important role in anti-Tembusu virus (TMUV) infection. However, laboratory of genetics and physiology 2 (LGP2), the third member of RLRs family, the regulatory function on antiviral innate immunity of MDA5 is currently unclear. In this study, we investigated the subcellular localization of duck LGP2 (duLGP2) and confirmed that it is an important regulator of the duMDA5-mediated host innate antiviral immune response. The present experimental data demonstrate that the overexpression of duLGP2 inhibits duMDA5 downstream transcriptional factor (IRF-7, IFN-β, and NF-κB) promoter activity, and duMDA5-mediated type I IFNs and ISGs expression were significantly suppressed by duLGP2 regardless of viral infection in vitro. The inhibition of duLGP2 on the antiviral activity of duMDA5 ultimately leads to an increase in viral replication. However, the overexpression of duLGP2 promotes expression of mitochondrial antiviral-signaling protein (MAVS) and duMDA5-mediated proinflammatory cytokines. This study provides a new rationale support for the duLGP2 regulates duMDA5-mediated anti-viral immune signaling pathway theory in duck.

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http://dx.doi.org/10.1016/j.vetmic.2021.109281DOI Listing

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