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  2. PRV-encoded UL13 protein kinase acts as an antagonist of innate immunity by targeting IRF3-signaling pathways

PRV-encoded UL13 protein kinase acts as an antagonist of innate immunity by targeting IRF3-signaling pathways

  • Vet Microbiol. 2020 Nov;250:108860. doi: 10.1016/j.vetmic.2020.108860.
Lin Lv 1 Mingzhu Cao 1 Juan Bai 1 Ling Jin 2 Xianwei Wang 1 Yanni Gao 1 Xuewei Liu 1 Ping Jiang 3
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
  • 2 Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
  • 3 Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health & Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China. Electronic address: jiangp@njau.edu.cn.
Abstract

Pseudorabies virus (PRV), a porcine alphaherpesvirus, causes neurological disorders and reproductive failure in swine. It is capable of avoiding host Antiviral responses, resulting in viral latency in infected Animals. The mechanisms by which many PRV proteins help the virus to evade immune surveillance are poorly understood. In this study, we found that the PRV protein kinase, UL13, inhibits the IFN-β signaling pathway by targeting interferon regulatory factor 3 (IRF3) for ubiquitination and degradation. PRV with mutant of UL13 is impaired in its ability to hinder IRF3 and interferon-β (IFN-β) activation, and has significantly less pathogenesis in mice that wild-type PRV. Our findings reveal an as yet undescribed mechanism utilized by PRV to evade host immune responses. PRV UL13 is a potential target for attenuated vaccines and Antiviral drugs.

Keywords

Alphaherpesviruses; IRF3; Innate immunity; Pseudorabies virus; UL13.

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