2. Academic Validation
  3. Pseudorabies virus VHS protein abrogates interferon responses by blocking NF-κB and IRF3 nuclear translocation

Pseudorabies virus VHS protein abrogates interferon responses by blocking NF-κB and IRF3 nuclear translocation

  • Virol Sin. 2024 May 30:S1995-820X(24)00078-6. doi: 10.1016/j.virs.2024.05.009.
Zhenfang Yan 1,  Jiayu Yue 1,  Yaxin Zhang 1,  Zhengyang Hou 1,  Dianyu Li 1,  Yanmei Yang 2,  Xiangrong Li 3,  Adi Idris 4,  Huixia Li 1,  Shasha Li 2,  Jingying Xie 5,  Ruofei Feng 6
Affiliations

Affiliations

  • 1 Key Laboratory of Biotechnology and Bioengineering of State Ethnic Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China.
  • 2 College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, China.
  • 3 Key Laboratory of Biotechnology and Bioengineering of State Ethnic Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; Engineering Research Center of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China.
  • 4 Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, Queensland, 4702, Australia.
  • 5 Key Laboratory of Biotechnology and Bioengineering of State Ethnic Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; College of Life Science and Engineering, Northwest Minzu University, Lanzhou, 730030, China. Electronic address: xjy_1314@126.com.
  • 6 Key Laboratory of Biotechnology and Bioengineering of State Ethnic Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; Gansu Tech Innovation Center of Animal Cell, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China; Engineering Research Center of Key Technology and Industrialization of Cell-based Vaccine, Ministry of Education, Biomedical Research Center, Northwest Minzu University, Lanzhou, 730030, China. Electronic address: fengruofei@xbmu.edu.cn.
PMID: 38823782 DOI: 10.1016/j.virs.2024.05.009
Abstract

Herpesviruses antagonize host Antiviral responses through a myriad of molecular strategies culminating in the death of the host cells. Pseudorabies virus (PRV) is a significant veterinary pathogen in pigs, causing neurological sequalae that ultimately lead to the animal's demise. PRV is known to trigger apoptotic cell death during the late stages of Infection. The virion host shutdown protein (VHS) encoded by UL41 plays a crucial role in the PRV Infection process. In this study, we demonstrate that UL41 inhibits PRV-induced activation of inflammatory cytokine and negatively regulates the cGAS-STING-mediated Antiviral activity by targeting IRF3, thereby inhibiting the translocation and phosphorylation of IRF3. Notably, mutating the conserved amino acid sites (E192, D194, and D195) in the RNase domain of UL41 or knocking down UL41 inhibits the immune evasion of PRV, suggesting that UL41 may play a crucial role in PRV's evasion of the host immune response during Infection. These results enhance our understanding of how PRV structural proteins assist the virus in evading the host immune response.

Keywords

IRF3; Interferon; Pseudorabies virus (PRV); UL41; cGAS-STING.

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