MiR-124 attenuates Japanese encephalitis virus replication by targeting DNM2

Songbai Yang,Ayong Zhao,Shuhong Zhao,Yue Pei,Mengjin Zhu,Xinyun Li

doi:10.1186/s12985-016-0562-y

Abstract

BackgroundJapanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes acute viral encephalitis in humans. Pigs are important amplifier hosts of JEV. Emerging evidence indicates that host microRNAs (miRNAs) play key roles in modulating viral infection and pathogenesis. However, mechanistic studies delineating the roles of miRNAs in regulating host-JEV interactions remain scarce.ResultsIn this study, we demonstrated that miR-124 inhibited JEV replication in porcine kidney epithelial PK15 cells. Furthermore, using bioinformatics tools, we identified dynamin2 (DNM2), a GTPase responsible for vesicle scission, as a target of miR-124. Small interfering RNA (siRNA) depletion studies inicated that dynamin2 was required for efficient JEV replication. We also demonstrated that upregulation of miR-124 expression corresponded to decreased expression of its target, DNM2, in the JEV-infected PK15 cells.ConclusionsOverall, these results suggest the importance of miR-124 in modulating JEV replication and provide a scientific basis for using cellular miRNAs in anti-JEV therapies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-016-0562-y) contains supplementary material, which is available to authorized users.

Highlights

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes acute viral encephalitis in humans
MicroRNAs are small non-coding RNAs of approximately 22 nucleotides in length, which play a crucial role in the post-transcriptional regulation of genes involved in fundamental biological processes, including cell differentiation, proliferation, apoptosis and cell signaling [10, 11]. miRNAs regulate gene expression by guiding the RNA-induced silencing complex (RISC) to partially complementary sites within the 3’ UTR of target mRNAs via their seed region [12]. miRNAs have been shown to regulate the host antiviral response by altering the expression of host genes required for virus replication and antiviral response [13,14,15,16] or by directly targeting viral genomes and/or transcripts. [17,18,19,20]
We show that expression of miR-124 is upregulated in response to JEV infection and that this results in the suppression of the target gene, DNM2, which is required for virus replication

Summary

Introduction

Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes acute viral encephalitis in humans. Emerging evidence indicates that host microRNAs (miRNAs) play key roles in modulating viral infection and pathogenesis. Mechanistic studies delineating the roles of miRNAs in regulating host-JEV interactions remain scarce. Pigs act as amplifying hosts of JEV; the domestic pig was considered to be a risk factor in the transmission of the disease to humans [3, 4]. The primary symptoms of pigs infected with JEV are fetal abortion and stillbirth in infected sows and MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides in length, which play a crucial role in the post-transcriptional regulation of genes involved in fundamental biological processes, including cell differentiation, proliferation, apoptosis and cell signaling [10, 11]. The primary symptoms of pigs infected with JEV are fetal abortion and stillbirth in infected sows and MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides in length, which play a crucial role in the post-transcriptional regulation of genes involved in fundamental biological processes, including cell differentiation, proliferation, apoptosis and cell signaling [10, 11]. miRNAs regulate gene expression by guiding the RNA-induced silencing complex (RISC) to partially complementary sites within the 3’ UTR of target mRNAs via their seed region [12]. miRNAs have been shown to regulate the host antiviral response by altering the expression of host genes required for virus replication and antiviral response [13,14,15,16] or by directly targeting viral genomes and/or transcripts. [17,18,19,20]

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