MiR-4334-5p Facilitates Foot and Mouth Disease Virus Propagation by Suppressing Interferon Pathways via Direct Targeting ID1.

Yanxue Wang,Kailing Wang,Tingting Ren,Yongguang Zhang,Yuefeng Sun,Haotai Chen,Lei Liu

doi:10.3390/genes11101136

Abstract

Emerging evidence indicates that the host microRNAs (miRNAs) are important intracellular regulators and play pivotal roles in intricate host-pathogen interaction networks. In our previous studies, ssc-microRNA-4334-5p (miR-4334-5p) was identified as a differentially expressed miRNA in microarray-based miRNAs profiling experiment, but whether miR-4334-5p regulates foot and mouth disease virus (FMDV) propagation is less understood. Here, we demonstrated that miR-4334-5p expression level was up-regulated shortly after FMDV infection, transfection of miR-4334-5p mimics promoted, while inhibitor transfection suppressed FMDV replication correspondingly. Further bioinformatic analysis and experimental study suggested ID1 was the direct target of miR-4334-5p, suppressing FMDV replication by regulating interferon (IFN) pathways. These findings shed light on microRNAs-ID1-interferon axis in regulating FMDV replication.

Highlights

Foot and mouth disease is an acute and highly contagious disease, caused by foot and mouth disease virus (FMDV), which mainly occurred in cloven-hoofed animals, such as cattle, sheep, goats and swine
PK-15 cells were challenged by FMDV (O/BY/CHA/2010) at 0.1 multiplicity of infection (MOI) or 1 MOI, separately. quantitative real-time PCR (qRT-PCR) was applied to to quantify quantify miR-4334-5p miR‐4334‐5p expression
Compared with the control groups, TNFα, OAS and ISG54 expression was suppressed after FMDV infection (Figure 5C–E). These results clearly proved that miR-4334-5p repressed interferon production and antiviral genes expression during FMDV infection

Summary

Introduction

Foot and mouth disease is an acute and highly contagious disease, caused by foot and mouth disease virus (FMDV), which mainly occurred in cloven-hoofed animals, such as cattle, sheep, goats and swine. The clinical symptoms in infected animals are usually shown as the vesicles formation in the mouth, nose, tongue, and skin between the claws of the feet [1]. FMDV is a member of the aphthovirus genus of the family Picornaviridae, and the genome RNA is ~8.5 kb with positive strand. The polyprotein is translated by the viral RNA, and subsequently cleaved into four structural proteins (VP1, VP2, VP3 and VP4), and eight nonstructural proteins (leader protein (Lpro ), 2A, 2B, 2C, 3A, 3B, 3Cpro and and proinflammatory cytokines is initiated, and the host protective immune response is followed; establishing a balance of the host against viral infection. According to the previous studies, Lpro , 3Cpro and VP3 of

Methods

Results

Conclusion