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Published on: April 21, 2015
Identification of cellular microRNA miR-188-3p with broad-spectrum anti-influenza A virus activity
Huan Cui1,2, Chunmao Zhang1, Zongzheng Zhao1
1Institute of Military Veterinary, Academy of Military Medical Sciences, 666 West Liuying Road, Changchun, 130122, Jilin, China.
Background:
Influenza A virus (IAV) continues to pose serious threats to public health. The current prophylaxis and therapeutic interventions for IAV requires frequent changes due to the continuous antigenic drift and antigenic shift of IAV. Emerging evidence indicates that the host microRNAs (miRNAs) play critical roles in intricate host-pathogen interaction networks. Cellular miRNAs may directly target virus to inhibit its infection and be developed as potential anti-virus drugs.
Methods:
In this study, we established a broad-spectrum anti-IAV miRNA screening method using miRanda software. The screened miRNAs were further verified by luciferase assay, viral protein expression assay and virus replication assay.
Results:
Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p and miR-769-3p), targeting 99.96, 95.31, 92.9, 94.58 and 97.24% of human IAV strains recorded in NCBI, respectively, were chosen for further experimental verification. Finally, we found that miR-188-3p downregulated PB2 expression at both mRNA and protein levels by directly targeted the predicted sites on PB2 and effectively inhibited the replication of IAV (H1N1, H5N6 and H7N9) in A549 cells.
Conclusions:
This is the first report screening cellular miRNAs that broad-spectrum inhibiting IAV infection. These findings suggested that cellular miR-188-3p could be used for RNAi-mediated anti-IAV therapeutic strategies.
Insights
This study identifies cellular microRNAs (miRNAs) as potential broad-spectrum antivirals against Influenza A virus (IAV). miR-188-3p effectively inhibits IAV replication by targeting the PB2 protein, offering a novel therapeutic strategy.
Area of Science:
- Virology
- Molecular Biology
- Genetics
Background:
- Influenza A virus (IAV) poses a significant public health threat due to rapid evolution.
- Current antiviral strategies for IAV require frequent updates.
- Host microRNAs (miRNAs) are increasingly recognized for their role in host-pathogen interactions and potential as antiviral agents.
Purpose of the Study:
- To develop a broad-spectrum screening method for identifying cellular miRNAs with anti-IAV activity.
- To evaluate the potential of identified miRNAs as therapeutic agents against IAV.
Main Methods:
- A screening method using miRanda software was established to identify anti-IAV miRNAs.
- Selected miRNAs were validated through luciferase assays, viral protein expression analysis, and virus replication assays.
- The efficacy of miR-188-3p against IAV strains (H1N1, H5N6, H7N9) was assessed in A549 cells.
Main Results:
- Five cellular miRNAs (miR-188-3p, miR-345-5p, miR-3183, miR-15-3p, miR-769-3p) showed high targeting efficiency against human IAV strains.
- miR-188-3p was found to directly target the PB2 gene, downregulating its mRNA and protein expression.
- miR-188-3p significantly inhibited the replication of multiple IAV subtypes (H1N1, H5N6, H7N9).
Conclusions:
- This study presents the first report of screening cellular miRNAs for broad-spectrum inhibition of IAV.
- Cellular miR-188-3p demonstrates significant potential as a therapeutic agent for RNAi-mediated anti-IAV strategies.
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