Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation

Jingying Xie; Xiangbo Zhang; Lei Chen; Yingjie Bi; Adi Idris; Shujuan Xu; Xiangrong Li; Yong Zhang; Ruofei Feng

doi:10.3389/fmicb.2021.761282

Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation

Front Microbiol. 2021 Oct 22:12:761282. doi: 10.3389/fmicb.2021.761282. eCollection 2021.

Authors

Jingying Xie^{1

2}, Xiangbo Zhang¹, Lei Chen¹, Yingjie Bi¹, Adi Idris³, Shujuan Xu¹, Xiangrong Li¹, Yong Zhang², Ruofei Feng¹

Affiliations

¹ Key Laboratory of Biotechnology and Bioengineering of State Ethnic Affairs Commission, Biomedical Research Center, Northwest Minzu University, Lanzhou, China.
² College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.
³ Menzies Health Institute Queensland, School of Pharmacy and Medical Science, Griffith University, Southport, QLD, Australia.

Abstract

Pseudorabies virus is a typical swine alphaherpesvirus, which can cause obvious neurological disorders and reproductive failure in pigs. It is capable of evading host antiviral immune response. However, the mechanism by which many PRV proteins assist the virus to evade innate immunity is not fully understood. This study identified PRV US3 protein as a crucial antagonistic viral factor that represses interferon beta (IFN-β) expression. A in-depth study showed that US3 protein restricted type I IFN production by targeting interferon regulatory factor 3 (IRF3), a key molecule required for type I IFN induction. Additionally, US3 protein interacted with IRF3, degraded its protein expression to block the phosphorylation of IRF3. These findings suggested a novel strategy utilized by PRV to inhibit IFN-β production and escape the host innate immunity.

Keywords: IFN-β; IRF3; US3 protein; innate immunity; pseudorabies virus.