Krüppel-like factor 4 negatively regulates cellular antiviral immune response

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. Access through

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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). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * College of Life Sciences,

Medical Research Institute, Wuhan University, Wuhan, China Wei-Wei Luo, Huan Lian, Bo Zhong, Hong-Bing Shu & Shu Li Authors * Wei-Wei Luo View author publications You can also search for

this author inPubMed Google Scholar * Huan Lian View author publications You can also search for this author inPubMed Google Scholar * Bo Zhong View author publications You can also search

for this author inPubMed Google Scholar * Hong-Bing Shu View author publications You can also search for this author inPubMed Google Scholar * Shu Li View author publications You can also

search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Shu Li. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download

citation * Received: 31 July 2014 * Revised: 20 November 2014 * Accepted: 20 November 2014 * Published: 22 December 2014 * Issue Date: January 2016 * DOI:

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currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * innate antiviral response * KLF4 * promoter *

translocation * type I interferons