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Updated: May 10, 2026

MicroRNA-based Regulation of Picornavirus Tropism
Published on: February 6, 2017
Identification of Host Kinase Genes Required for Influenza Virus Replication and the Regulatory Role of MicroRNAs
Abhijeet Bakre1, Lauren E Andersen, Victoria Meliopoulos
1Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
Abstract:
Human protein kinases (HPKs) have profound effects on cellular responses. To better understand the role of HPKs and the signaling networks that influence influenza virus replication, a small interfering RNA (siRNA) screen of 720 HPKs was performed. From the screen, 17 HPKs (NPR2, MAP3K1, DYRK3, EPHA6, TPK1, PDK2, EXOSC10, NEK8, PLK4, SGK3, NEK3, PANK4, ITPKB, CDC2L5 (CDK13), CALM2, PKN3, and HK2) were validated as essential for A/WSN/33 influenza virus replication, and 6 HPKs (CDK13, HK2, NEK8, PANK4, PLK4 and SGK3) were identified as vital for both A/WSN/33 and A/New Caledonia/20/99 influenza virus replication. These HPKs were found to affect multiple host pathways and regulated by miRNAs induced during infection. Using a panel of miRNA agonists and antagonists, miR-149* was found to regulate NEK8 expression, miR-548d-3p was found to regulate MAPK1 transcript expression, and miRs -1228 and -138 to regulate CDK13 expression. Up-regulation of miR-34c induced PLK4 transcript and protein expression and enhanced influenza virus replication, while miR-34c inhibition reduced viral replication. These findings identify HPKs important for influenza viral replication and show the miRNAs that govern their expression.
Insights
This study identified essential human protein kinases (HPKs) crucial for influenza virus replication. MicroRNAs (miRNAs) were found to regulate these HPKs, offering new targets for antiviral strategies.
Area of Science:
- Virology
- Molecular Biology
- Cellular Signaling
Background:
- Human protein kinases (HPKs) play critical roles in cellular processes.
- Understanding host factors influencing influenza virus replication is vital for developing antiviral therapies.
Purpose of the Study:
- To identify HPKs essential for influenza A virus replication.
- To investigate the role of microRNAs (miRNAs) in regulating these HPKs during infection.
Main Methods:
- A small interfering RNA (siRNA) screen of 720 HPKs was conducted.
- Validation of identified HPKs for influenza virus replication.
- Analysis of miRNA regulation on specific HPKs using agonists and antagonists.
Main Results:
- 17 HPKs were essential for A/WSN/33 influenza virus replication.
- 6 HPKs were vital for both A/WSN/33 and A/New Caledonia/20/99 influenza virus replication.
- Specific miRNAs (miR-149*, miR-548d-3p, miR-1228, miR-138, miR-34c) were shown to regulate key HPKs (NEK8, MAPK1, CDK13, PLK4).
- Upregulation of miR-34c enhanced viral replication by inducing PLK4 expression.
Conclusions:
- This study identifies critical HPKs involved in influenza virus replication.
- MiRNAs are key regulators of these HPKs, presenting potential therapeutic targets for influenza.
- The findings provide insights into host-virus interactions and miRNA-mediated regulation of viral replication.
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