Bovine cyclic GMP-AMP synthase recognizes exogenous double-stranded DNA and activates the STING-depended interferon β production pathway

Haiyue Dai; Yixiao Wang; Zhenying Fan; Yongli Guo; Jiaqi Chen; Ye Meng; Xin Tong; Mingchun Gao; Junwei Wang

doi:10.1016/j.dci.2022.104567

Bovine cyclic GMP-AMP synthase recognizes exogenous double-stranded DNA and activates the STING-depended interferon β production pathway

Dev Comp Immunol. 2023 Feb:139:104567. doi: 10.1016/j.dci.2022.104567. Epub 2022 Oct 10.

Authors

Haiyue Dai¹, Yixiao Wang², Zhenying Fan², Yongli Guo², Jiaqi Chen², Ye Meng², Xin Tong², Mingchun Gao³, Junwei Wang⁴

Affiliations

¹ Heilongjiang Provincial Key Laboratory of Zoonosis, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China; Key Laboratory of Animal Epidemiology and Zoonosis, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, China.
² Heilongjiang Provincial Key Laboratory of Zoonosis, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China.
³ Heilongjiang Provincial Key Laboratory of Zoonosis, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: gaomingchun@neau.edu.cn.
⁴ Heilongjiang Provincial Key Laboratory of Zoonosis, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: jwwang@neau.edu.cn.

PMID: 36228808
DOI: 10.1016/j.dci.2022.104567

Abstract

The cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) recognizes exogenous double-stranded DNA and produces 2'3'-cyclic GMP-AMP (2'3'-cGAMP), activating the stimulator of interferon genes (STING) and innate immunity. Bovine cGAS functions remain poorly understood. Herein, the coding sequence of the bo-cGAS gene was obtained and its recognition function was investigated. Bo-cGAS consists of 1542 nucleotides and the encoding acid sequence contained high sequence homology to that of other livestock. Bo-cGAS was localized in the endoplasmic reticulum and was abundant in the lung. Bo-cGAS and bo-STING coexistence significantly activated the IFN-β promotor. Synthesized 2'3'-cGAMP activated the STING-dependent pathway. Upon bo-cGAS recognition of poly(dA:dT) and bovine herpesvirus type 1 (BHV-1), Viperin transcription displayed the opposite time-dependent trend. Significant restriction of IFN-β transcription but augmentation of myxovirus resistance protein 1 (Mx1) and Viperin occurred during BHV-1 infection. Thus, bo-cGAS recognized exogenous double-stranded DNA and triggered the STING-dependent IFN-β production pathway.

Keywords: Bovine STING; Bovine cyclic GMP-AMP synthase; DNA recognition Signaling pathway; IFN-β production pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
DNA*
Interferon-beta* / genetics

Substances

cyclic guanosine monophosphate-adenosine monophosphate
DNA
Interferon-beta