miR-124 attenuates Japanese encephalitis virus replication by targeting DNM2

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.

Broad-Spectrum Inhibition of Respiratory Virus Infection by MicroRNA Mimics Targeting p38 MAPK Signaling

“…The RPPA study identified additional proteins that may be targeted by these miRNAs, such as miR-744 targeting of Akt or miR-124a and miR-24 suppression of GSK-3β, as both of these factors were previously shown to be important for influenza virus entry 56, 57. Other previously identified roles of these miRNAs in viral infection include miR-24 suppression of Kruppel-like factor 6, which is induced by RSV infection to induce cell-cycle arrest, 14 as well as the suppression of furin by miR-24, which is required for influenza virus activation, 58 and miR-124a attenuation of Japanese encephalitis virus (JEV) via targeting dynamin2, which is required for efficient JEV replication 59 . Therefore, it is highly probable that the broad-spectrum antiviral activity exhibited by these miRNA mimics is caused by their ability to downregulate multiple host factors that are essential for numerous DNA and RNA viral infections.…”

Exploitation of microRNAs by Japanese Encephalitis virus in human microglial cells

“…The growing number of reports have shown the dysregulation of microRNAs in various diseased conditions . We and others have reported the role of microRNA during JE neuroinflammation, where the virus impairs the function of microRNA and affect the down‐stream signaling in human brain microglial cells …”

“…Previously published reports by our and other's research group already demonstrated the role of microRNA in JEV infected microglial cells. 13,19,21…”

“…Several groups have reported the JEV‐mediated expression of miR‐301a suppress the production of type I Interferon (IFN‐type I) via IRF1 and SOCS5 and helps in virus propagation . The miR‐124 has been documented in modulating the JEV replication in PK15 cells via DNM2 (dynamin 2), which promotes virus endocytosis . The miR‐15b and miR‐155 have been implicated in modulating the JEV mediated inflammatory responses via RNF125 and SHIP‐1 in microglia.…”

“…18 The miR-124 has been documented in modulating the JEV replication in PK15 cells via DNM2 (dynamin 2), which promotes virus endocytosis. 19 The miR-15b and miR-155 have been implicated in modulating the JEV mediated inflammatory responses via RNF125 20 and SHIP-1 5 in microglia. In addition, JEV infection has been reported to modulate the expression of microRNA-19b-3p and induces pro-inflammatory responses in glial cells, thereby increasing pathogenesis.…”