Vu Thi Hao, Heo Jubi, Kang Suyeon, Kim Chaeeun, Lillehoj Hyun S, Hong Yeong Ho
Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea; Department of Biochemistry and Immunology, National Institute of Veterinary Research, Hanoi, 100000, Viet Nam.
Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea.
Dev Comp Immunol. 2023 Dec;149:104921. doi: 10.1016/j.dci.2023.104921. Epub 2023 Aug 21.
MicroRNAs play crucial roles in immune-related pathways in host animals. In this study, we aimed to investigate the systemic biological function of gga-miR-26a-5p, a chicken miRNA, in the immune responses to HPAIV H5N1 infection in the Vietnamese Ri chicken line. Our results showed a significant downregulation in gga-miR-26a expression in the lung tissue of Ri chickens during HPAIV H5N1 infection. Overexpression of gga-miR-26a and the reporter construct, either containing the wildtype or mutant melanoma differentiation-associated protein 5 (MDA5) 3' untranslated region (3' UTR)-luciferase, into a chicken fibroblast cell line, revealed that gga-miR-26a can act as a direct translational repressor of MDA5 by targeting the 3' UTRs. Additionally, miR-26a negatively regulated the expression of the signaling molecules related to the MDA5 signaling pathway, including MDA5, mitochondrial antiviral-signaling (MAVS), interferon regulatory factor 7 (IRF7), p38 mitogen-activated protein kinases, and nuclear factor-kappa B (NF-κB). Moreover, downstream of the IRF7 and NF-κB signaling pathway, the proinflammatory cytokines such as IL-1β, IFN-γ, IFN-α, IFN-β, and the interferon-stimulated gene (Mx1) were, likewise, downregulated by the overexpression of gga-miR-26a. These findings suggest that gga-miR-26a-5p serves as an important regulator in the MDA5 signaling pathway and antiviral response. Overall, our results contribute to an improved understanding of the biological functions of gga-miR-26a-5p, alongside the mechanisms underlying the MDA5 signaling pathway, and the antiviral response to HPAIV-H5N1 infection in chickens.
微小RNA在宿主动物的免疫相关通路中发挥着关键作用。在本研究中，我们旨在探究鸡微小RNA gga-miR-26a-5p在越南里鸡品系对高致病性禽流感病毒H5N1感染的免疫反应中的全身生物学功能。我们的结果显示，在高致病性禽流感病毒H5N1感染期间，里鸡肺组织中gga-miR-26a的表达显著下调。将gga-miR-26a和报告基因构建体（包含野生型或突变型黑色素瘤分化相关蛋白5（MDA5）的3'非翻译区（3'UTR）-荧光素酶）过表达至鸡成纤维细胞系中，结果表明gga-miR-26a可通过靶向3'UTR作为MDA5的直接翻译抑制因子。此外，miR-26a负向调节与MDA5信号通路相关的信号分子的表达，包括MDA5、线粒体抗病毒信号蛋白（MAVS）、干扰素调节因子7（IRF7）、p38丝裂原活化蛋白激酶和核因子κB（NF-κB）。此外，在IRF7和NF-κB信号通路的下游，促炎细胞因子如IL-1β、IFN-γ、IFN-α、IFN-β以及干扰素刺激基因（Mx1）同样因gga-miR-26a的过表达而下调。这些发现表明gga-miR-26a-5p在MDA5信号通路和抗病毒反应中起着重要调节作用。总体而言，我们的结果有助于更好地理解gga-miR-26a-5p的生物学功能，以及MDA5信号通路的潜在机制和鸡对高致病性禽流感病毒H5N1感染的抗病毒反应。
