Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity

Yanqiong Zhang; Zhe Ma; Ying Wang; Joshua Boyer; Guoxin Ni; Liang Cheng; Siyuan Su; Zhigang Zhang; Zhichuan Zhu; Jiayi Qian; Lishan Su; Qi Zhang; Blossom Damania; Pengda Liu

doi:10.1016/j.isci.2020.101463

Streptavidin Promotes DNA Binding and Activation of cGAS to Enhance Innate Immunity

iScience. 2020 Aug 14;23(9):101463. doi: 10.1016/j.isci.2020.101463. eCollection 2020 Sep 25.

Authors

Yanqiong Zhang^{1

2}, Zhe Ma¹, Ying Wang^{1

2}, Joshua Boyer², Guoxin Ni¹, Liang Cheng^{1

3}, Siyuan Su^{1

2}, Zhigang Zhang¹, Zhichuan Zhu^{1

2}, Jiayi Qian^{1

2}, Lishan Su^{1

3}, Qi Zhang², Blossom Damania^{1

3

4}, Pengda Liu^{1

2}

Affiliations

¹ Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
² Department of Biochemistry and Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
³ Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ University of North Carolina Center for AIDS Research, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Abstract

cGAS/STING signaling plays an essential role in sensing cytosolic DNA. cGAS activity is regulated by posttranslational modifications and binding partners. cGAS interactome largely includes mammalian or viral proteins. Whether and how bacterial proteins bind cGAS to modulate innate immunity remain elusive. Here, we found streptavidin, a secreted bacterial protein, selectively bound cGAS to promote DNA-induced cGAS activation and interferon-β production. Mechanistically, streptavidin enhanced DNA binding and cGAS phase separation, therefore facilitating cGAS activation. Using an HSV-1-infected mouse model, we found streptavidin nanoparticles facilitated HSV-1 clearance through improving innate immunity. Considering the clinical usage of streptavidin as an immune stimulant and drug delivery vehicle and its biotechnological usage for biotin-labeled protein purification and detection, our studies not only provide an example for a bacterial protein regulating cGAS activity but also suggest caution needs to be taken when using streptavidin in various applications given to its ability to induce innate immunity.

Keywords: Bacteriology; Immunology; Microbiology.

Abstract

Grants and funding