MicroRNA miR-155 inhibits cyprinid herpesvirus 3 replication via regulating AMPK-MAVS-IFN axis

• Published in: Developmental and comparative immunology Vol. 129; p. 104335
• Main Authors: Zhang, Chi, Wang, Qing, Liu, An-qi, Zhang, Chu, Liu, Lan-Hao, Lu, Long-Feng, Tu, Jiagang, Zhang, Yong-An
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.04.2022; Elsevier Science Ltd
• Subjects: 3' Untranslated Regions; AMP-activated protein kinase; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - pharmacology; AMPK; Animals; Antiviral agents; Antiviral Agents - pharmacology; Carp; Carps; Cell culture; Cell Line; CyHV-3; Drug development; Economic impact; Fish Diseases - virology; Herpesviridae; Herpesviridae Infections - genetics; Infections; Interferon; Interferon Type I - genetics; Kinases; MAVS; MicroRNAs; MicroRNAs - genetics; miR-155; miRNA; Mitochondria; mRNA; Non-coding RNA; Nucleotides; Proteins; Replication; Ribonucleic acid; RNA; RNA, Messenger - analysis; Type I interferon; Virus Replication - drug effects; AMPK; MAVS; Type I interferon; CyHV-3; miR-155
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2021.104335

Since emerged in the late 1990s, cyprinid herpesvirus 3 (CyHV-3) has caused huge economic losses in common and koi carp culture worldwide. Accumulating evidences suggest that teleost fish microRNA (miRNA), a class of non-coding RNA of ∼22 nucleotides, can participate in many cellular processes, especially in host antiviral defenses. However, the roles of miRNAs in CyHV-3 infection are still unclear. Here, using high-throughput miRNA sequencing and quantitative real-time PCR (qRT-PCR) verification, we found that miR-155 was significantly upregulated in common carp brain (CCB) cells upon CyHV-3 infection. Overexpression of miR-155 effectively inhibited CyHV-3 replication in CCB cells and promoted type I interferon (IFN–I) expression. Further study revealed that miR-155 targeted the 3′ untranslated region (UTR) of the mRNA of 5′AMP-activated protein kinase (AMPK), and that AMPK could interact with and degrade the mitochondrial antiviral signaling protein (MAVS), resulting in the reduction of interferon (IFN) expression. Collectively, our results show that miR-155, induced by CyHV-3 infection, exhibits anti-CyHV-3 activity via regulating AMPK-MAVS-IFN axis, which will help design anti-CyHV-3 drugs. •We find that miR-155 inhibits CyHV-3 replication via promoting interferon expression.•We identify that the target gene of miR-155 is AMPK, and AMPK regulates IFN expression.•We find that AMPK can interact with and degrade MAVS.