Dataset Information

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-? Expression via Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.

ABSTRACT: Snakehead vesiculovirus (SHVV), a new rhabdovirus isolated from diseased hybrid snakehead, has emerged as an important pathogen during the past few years in China with great economical losses in snakehead fish cultures. However, little is known about the mechanism of its pathogenicity. MicroRNAs are small noncoding RNAs that posttranscriptionally modulate gene expression and have been indicated to regulate almost all cellular processes. Our previous study has revealed that miR-214 was downregulated upon SHVV infection.The overexpression of miR-214 in striped snakehead (SSN-1) cells inhibited SHVV replication and promoted IFN-? expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-? expression. These findings suggested that miR-214 negatively regulated SHVV replication probably through positively regulating IFN-? expression. Further investigation revealed that adenosine 5'-monophosphate-activated protein kinase (AMPK) was a target gene of miR-214. Knockdown of AMPK by siRNA inhibited SHVV replication and promoted IFN-? expression, suggesting that cellular AMPK positively regulated SHVV replication and negatively regulated IFN-? expression. Moreover, we found that siAMPK-mediated inhibition of SHVV replication could be partially restored by miR-214 inhibitor, indicating that miR-214 inhibited SHVV replication at least partially via targeting AMPK.The findings of this study complemented our early study, and provide insights for the mechanism of SHVV pathogenicity. SHVV infection downregulated miR-214, and in turn, the downregulated miR-214 increased the expression of its target gene AMPK, which promoted SHVV replication via reducing IFN-? expression. It can therefore assume that cellular circumstance with low level of miR-214 is beneficial for SHVV replication and that SHVV evades host antiviral innate immunity through decreasing IFN-? expression via regulating cellular miR-214 expression.

SUBMITTER: Zhang C

PROVIDER: S-EPMC5732478 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression <i>via</i> Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.

Zhang Chi C Feng Shuangshuang S Zhang Wenting W Chen Nan N Hegazy Abeer M AM Chen Wenjie W Liu Xueqin X Zhao Lijuan L Li Jun J Lin Li L Tu Jiagang J

Frontiers in immunology 20171211

<h4>Background</h4>Snakehead vesiculovirus (SHVV), a new rhabdovirus isolated from diseased hybrid snakehead, has emerged as an important pathogen during the past few years in China with great economical losses in snakehead fish cultures. However, little is known about the mechanism of its pathogenicity. MicroRNAs are small noncoding RNAs that posttranscriptionally modulate gene expression and have been indicated to regulate almost all cellular processes. Our previous study has revealed that miR ...[more]

PMID: 29312306

Similar Datasets

Project description:Snakehead vesiculovirus (SHVV), a kind of fish rhabdovirus isolated from diseased hybrid snakehead fish, has caused great economic losses in snakehead fish culture in China. The large (L) protein, together with its cofactor phosphoprotein (P), forms a P/L polymerase complex and catalyzes the transcription and replication of viral genomic RNA. In this study, the cellular heat shock protein 90 (Hsp90) was identified as an interacting partner of SHVV L protein. Hsp90 activity was required for the stability of SHVV L because Hsp90 dysfunction caused by using its inhibitor destabilized SHVV L and thereby suppressed SHVV replication via reducing viral RNA synthesis. SHVV L expressed alone was detected mainly in the insoluble fraction, and the insoluble L was degraded by Hsp90 dysfunction through the proteasomal pathway, while the presence of SHVV P promoted the solubility of SHVV L and the soluble L was degraded by Hsp90 dysfunction through the autophagy pathway. Collectively, our data suggest that Hsp90 contributes to the maturation of SHVV L and ensures the effective replication of SHVV, which exhibits an important anti-SHVV target. This study will help us to understand the role of Hsp90 in stabilizing the L protein and regulating the replication of negative-stranded RNA viruses. IMPORTANCE It has long been proposed that cellular proteins are involved in viral RNA synthesis via interacting with the viral polymerase protein. This study focused on identifying cellular proteins interacting with the SHVV L protein, studying the effects of their interactions on SHVV replication, and revealing the underlying mechanisms. We identified Hsp90 as an interacting partner of SHVV L and found that Hsp90 activity was required for SHVV replication. Hsp90 functioned in maintaining the stability of SHVV L. Inhibition of Hsp90 activity with its inhibitor degraded SHVV L through different pathways based on the solubility of SHVV L due to the presence or absence of SHVV P. Our data provide important insights into the role of Hsp90 in SHVV polymerase maturation, which will help us to understand the polymerase function of negative-stranded RNA viruses.

Dataset Information

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-? Expression via Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.

Publications

MicroRNA miR-214 Inhibits Snakehead Vesiculovirus Replication by Promoting IFN-α Expression <i>via</i> Targeting Host Adenosine 5'-Monophosphate-Activated Protein Kinase.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets