Abstract
Innate immunity provides immediate defense against viral infection. Influenza A virus (IAV) is able to get past the first line of defense. Elucidation of the molecular interaction between influenza factors and the newly recognized host players in the innate response might help in our understanding of the root causes of virulence and pathogenicity of IAV. In this study, we show that expression of miR-26a leads to a significant inhibition of IAV replication. miR-26a does not directly target IAV genome. Instead, miR-26a activates the type I interferon (IFN) signaling pathway and promotes the production of IFN-stimulated genes, thus suppressing viral replication. Furthermore, ubiquitin-specific protease 3 (USP3), a negative regulator of type I IFN pathway, is targeted by miR-26a upon IAV challenge. However, miR-26a is significantly downregulated during IAV infection. Thus, downregulation of miR-26a is a new strategy evolved by IAV to counteract cellular antiviral responses. Our findings indicate that delivery of miR-26a may be a potential strategy for anti-IAV therapies.
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Acknowledgments
This work was supported by grants from the National Basic Research Program of China (973 Program, No. 2012CB518900) and the Beijing Natural Science Foundation (No. 7122109).
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GSJ, SLP, and HWL designed the study. GSJ, LJD, SLP, and WJX carried out the experiments. GSJ, LJD, SLP, WJX, and HWL analyzed the data. GSJ and LJD wrote the paper. All authors have read and approved the final manuscript
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The authors declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.
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Gao, S., Li, J., Song, L. et al. Influenza A virus-induced downregulation of miR-26a contributes to reduced IFNα/β production. Virol. Sin. 32, 261–270 (2017). https://doi.org/10.1007/s12250-017-4004-9
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DOI: https://doi.org/10.1007/s12250-017-4004-9