2. Academic Validation
  3. Inhibition of histone deacetylase 1 suppresses pseudorabies virus infection through cGAS-STING antiviral innate immunity

Inhibition of histone deacetylase 1 suppresses pseudorabies virus infection through cGAS-STING antiviral innate immunity

  • Mol Immunol. 2021 Aug;136:55-64. doi: 10.1016/j.molimm.2021.05.012.
Yu-Kun Guo 1,  Sheng-Li Ming 1,  Lei Zeng 1,  Wen-Ru Chang 1,  Jia-Jia Pan 1,  Chao Zhang 1,  Bo Wan 2,  Jiang Wang 3,  Yu Su 4,  Guo-Yu Yang 5,  Bei-Bei Chu 6
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, PR China.
  • 2 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China.
  • 3 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China.
  • 4 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China. Electronic address: sunyu95@163.com.
  • 5 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China. Electronic address: haubiochem@163.com.
  • 6 College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, PR China; Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture and Rural Affairs of the People's Republic of China, PR China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, PR China. Electronic address: chubeibei@henau.edu.cn.
PMID: 34087624 DOI: 10.1016/j.molimm.2021.05.012
Abstract

Pseudorabies virus (PRV) is an enveloped double-stranded DNA virus that is the etiological agent of Aujeszky's disease in pigs. Vaccination is currently available to prevent PRV Infection, but there is still an urgent need for new strategies to control this infectious disease. Histone deacetylases (HDACs) are epigenetic regulators that regulate the histone tail, chromatin conformation, protein-DNA interaction and even transcription. Viral transcription and protein activities are intimately linked to regulation by histone acetyltransferases and HDACs that remodel chromatin and regulate gene expression. We reported here that genetic and pharmacological inhibition of HDAC1 significantly influenced PRV replication. Moreover, we demonstrated that inhibition of HDAC1 induced a DNA damage response and Antiviral innate immunity. Mechanistically, the HDAC1 inhibition-induced DNA damage response resulted in the release of double-strand DNA into the cytosol to activate Cyclic GMP-AMP Synthase and the downstream STING/TBK1/IRF3 innate immune signaling pathway. Our results demonstrate that an HDAC1 Inhibitor may be used as a new strategy to prevent Aujeszky's disease in pigs.

Keywords

DNA damage; Histone deacetylase1; Innate immunity; Pseudorabies virus.

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