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

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

  • Dev Comp Immunol. 2022 Oct 10;104567. doi: 10.1016/j.dci.2022.104567.
Haiyue Dai 1,  Yixiao Wang 2,  Zhenying Fan 2,  Yongli Guo 2,  Jiaqi Chen 2,  Ye Meng 2,  Xin Tong 2,  Mingchun Gao 3,  Junwei Wang 4
Affiliations

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: [email protected].
  • 4 Heilongjiang Provincial Key Laboratory of Zoonosis, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Northeast Agricultural University, Harbin, 150030, China. Electronic address: [email protected].
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.

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