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-α expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-α expression. These findings suggested that miR-214 negatively regulated SHVV replication probably through positively regulating IFN-α 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-α expression, suggesting that cellular AMPK positively regulated SHVV replication and negatively regulated IFN-α 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-α 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-α expression via regulating cellular miR-214 expression.
Highlights
MicroRNAs are a class of small (~22 nt) noncoding RNAs that posttranscriptionally degrade and/or suppress translation of target mRNAs through base pairing between the “seed sequences” (2–8 nt at the 5′ end) of miRNAs and the target transcripts [1,2,3,4,5]
Striped snakehead (SSN)-1 cells were transfected with miR-214 mimic, negative control (NC) mimic, miR-214 inhibitor, or NC inhibitor, followed by Snakehead vesiculovirus (SHVV) infection
At 24 h poi, it was apparent from Figures 1B,E that G protein expression was decreased by about 50% or increased to about 2.5-fold when the cells were transfected with miR-214 mimic or miR-214 inhibitor, respectively
Summary
MicroRNAs (miRNAs) are a class of small (~22 nt) noncoding RNAs that posttranscriptionally degrade and/or suppress translation of target mRNAs through base pairing between the “seed sequences” (2–8 nt at the 5′ end) of miRNAs and the target transcripts [1,2,3,4,5]. Our previous study has revealed that SHVV infection downregulated miR-214 [14], and in turn, miR-214 could inhibit SHVV production by targeting viral N and P [15]. It is unclear whether miR-214 can regulate SHVV replication via targeting host factors that are required for SHVV replication. 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. Results: The overexpression of miR-214 in striped snakehead (SSN-1) cells inhibited SHVV replication and promoted IFN-α expression, while miR-214 inhibitor facilitated SHVV replication and reduced IFN-α expression. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
