MiR-3470b promotes bovine ephemeral fever virus replication via directly targeting mitochondrial antiviral signaling protein (MAVS) in baby hamster Syrian kidney cells

Abstract

BackgroundBovine ephemeral fever virus (BEFV), the causative agent of bovine ephemeral fever, is an economically important pathogen of cattle and water buffalo. MicroRNAs (miRNAs) are endogenous 21-23 nt small non-coding RNA molecules that binding to a multiple of target mRNAs and functioning in the regulation of viral replication including the miRNA-mediated antiviral defense. However, the reciprocal interaction between bovine ephemeral fever virus replication and host miRNAs still remain poorly understood. The aim of our study herein was to investigate the exact function of miR-3470b and its molecular mechanisms during BEFV infection.ResultsIn this study, we found a set of microRNAs induced by BEFV infection using small RNA deep sequencing, and further identified BEFV infection could significantly up-regulate the miR-3470b expression in Baby Hamster Syrian Kidney cells (BHK-21) after 24 h and 48 h post-infection (pi) compared to normal BHK-21 cells without BEFV infection. Additionally, the target association between miR-3470b and mitochondrial antiviral signaling protein (MAVS) was predicted by target gene prediction tools and further validated using a dual-luciferase reporter assay, and the expression of MAVS mRNA and protein levels was negatively associated with miR-3470b levels. Furthermore, the miR-3470b mimic transfection significantly contributed to increase the BEFV N mRNA, G protein level and viral titer, respectively, whereas the miR-3470b inhibitor had the opposite effect on BEFV replication. Moreover, the overexpression of MAVS or silencing of miR-3470b by its inhibitors suppressed BEFV replication, and knockdown of MAVS by small interfering RNA also promoted the replication of BEFV.ConclusionsOur findings is the first to reveal that miR-3470b as a novel host factor regulates BEFV replication via directly targeting the MAVS gene in BHK-21 cells and may provide a potential strategy for developing effective antiviral therapy.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1366-6) contains supplementary material, which is available to authorized users.

SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy

“…CoV RNA can be recognized by RIG-I-like receptors (RLRs), including retinoic acid-inducible gene I (RIG-I) and/or melanoma differentiation gene 5 (MDA5), in the cytoplasm [ 19 ]. After activation, RIG-I and MDA5 can interact with the adapter mitochondrial antiviral signaling protein (MAVS, also termed IPS-1, VISA, and Cardif) [ 16 , 20 ]. Subsequently, MAVS recruits two IKK-related kinases, TANK-binding kinase 1 (TBK1) and inducible IκB kinase (IKKi), leading to activation of the transcription factors interferon regulatory factor 3/7 (IRF3/7) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [ 21 ].…”

Mitochondrial Dynamics Imbalance: A Strategy for Promoting Viral Infection

“…Subsequently, it was found that these two miRNAs also downregulated some mitochondrial metabolism-related proteins and a solute carrier protein SCL-25 A-12, which can act on MAVS downstream, further destroying the antiviral immune response of mitochondria ( Yasukawa et al, 2020 ). Another miRNA (Mir-3470b) was upregulated after infection with bovine ephemeral fever virus (BEFV) and promoted viral replication by targeting MAVS to inhibit antiviral signal transduction ( Hou et al, 2018 ). In recent years, the regulation of miRNA has become a research hotspot, and literature has reported the induction or protection of miRNA during the occurrence of various diseases ( Du et al, 2019 ; Kumar et al, 2019 ), which suggests that different miRNAs may be the key targets for future treatment of various diseases.…”

Mitochondrial antiviral signaling protein: a potential therapeutic target in renal disease

“…reported that miR-3470b directly targets MAVS 3’-UTR in Bovine ephemeral fever virus infection. In that study, the authors discovered that the overexpression of miR-3470b resulted in a marked decrease in MAVS at both the transcriptional and protein levels, thereby suppressing the antiviral response ( 85 ). Further, miR-3570 negatively regulates rhabdovirus-triggered production of type I interferons by targeting MAVS in miiuy croaker macrophages, thus facilitating viral replication ( 86 ).…”