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Krüppel-like factor 4 negatively regulates cellular antiviral immune response

Cellular & Molecular Immunology volume 13, pages 65–72 (2016)Cite this article

Abstract

Viral infection triggers activation of the transcription factors NF-κB and IRF3, which collaborate to induce the expression of type I interferons (IFNs) and elicit innate antiviral response. In this report, we identified Krüppel-like factor 4 (KLF4) as a negative regulator of virus-triggered signaling. Overexpression of KLF4 inhibited virus-induced activation of ISRE and IFN-β promoter in various types of cells, while knockdown of KLF4 potentiated viral infection-triggered induction of IFNB1 and downstream genes and attenuated viral replication. In addition, KLF4 was found to be localized in the cytosol and nucleus, and viral infection promoted the translocation of KLF4 from cytosol to nucleus. Upon virus infection, KLF4 was bound to the promoter of IFNB gene and inhibited the recruitment of IRF3 to the IFNB promoter. Our study thus suggests that KLF4 negatively regulates cellular antiviral response.

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Acknowledgements

We thank members of our laboratory for technical help and stimulating discussions. This work was supported by grants from the Ministry of Science and Technology of China (2012CB910201) and the National Natural Science Foundation of China (31130020, 31371427, 31101019 and 31221061).

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  1. College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan, China

    Wei-Wei Luo, Huan Lian, Bo Zhong, Hong-Bing Shu & Shu Li

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  1. Wei-Wei Luo
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  2. Huan Lian
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Correspondence to Shu Li.

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Luo, WW., Lian, H., Zhong, B. et al. Krüppel-like factor 4 negatively regulates cellular antiviral immune response. Cell Mol Immunol 13, 65–72 (2016). https://doi.org/10.1038/cmi.2014.125

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