1. Academic Validation
  2. Duck plague virus ICP27 protein suppresses IFN-β production by dual targeting of DNA- and RNA-sensing pathways

Duck plague virus ICP27 protein suppresses IFN-β production by dual targeting of DNA- and RNA-sensing pathways

  • Vet Microbiol. 2025 Aug 25:310:110696. doi: 10.1016/j.vetmic.2025.110696.
Mengya Zhang 1 Yumei He 1 Fengchen Jin 1 Mingshu Wang 2 Qiao Yang 2 Renyong Jia 2 Shun Chen 2 Bin Tian 2 Xumin Ou 2 Juan Huang 2 Di Sun 2 Dekang Zhu 2 Mafeng Liu 2 Shaqiu Zhang 2 Xin-Xin Zhao 2 Yu He 2 Zhen Wu 2 Ying Wu 3 Anchun Cheng 4
Affiliations

Affiliations

  • 1 Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang, China.
  • 2 Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, China; Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang, China.
  • 3 Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, China; Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang, China. Electronic address: wuy@sicau.edu.cn.
  • 4 Engineering Research Center of Southwest Animal Disease Prevention and Control Technology, Ministry of Education of the People's Republic of China, Chengdu 611130, China; International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Wenjiang, China; Avian Disease Research Center, College of Veterinary Medicine of Sichuan Agricultural University, Wenjiang, China. Electronic address: chenganchun@vip.163.com.
Abstract

Duck plague virus (DPV), an alphaherpesvirus causing severe economic losses in global waterfowl industries, adopts sophisticated strategies to subvert host Antiviral immunity. Here, we identify DPV ICP27 as a pivotal immune evasion protein that concurrently inhibits both DNA (cGAS-STING) and RNA (RIG-I/MDA5-MAVS) innate immune sensing pathways-a novel function unreported in avian herpesviruses. Through co-transfection and Infection assays in duck embryo fibroblasts (DEFs), we demonstrate that ICP27 suppresses key immune sensors' transcriptional and protein expression levels (STING, RIG-I) and the transcription factor IRF7. Co-immunoprecipitation confirms ICP27 binds to IRF7, impairing interferon regulatory functions, impairing interferon regulatory functions. Crucially, Infection with ICP27-knockout DPV (DPV-ΔICP27) significantly enhances IFN-β, IL-6, Mx, and OASL expression compared to wild-type virus. Phylogenetic analyses reveal conserved yet species-specific functional divergence of ICP27 across herpesviruses. Our findings identify a unique "multi-target cooperative suppression" mechanism employed by DPV, which enhances our understanding of avian herpesviral immune evasion and offers potential targets for developing novel Antiviral strategies.

Keywords

CGAS-STING/RIG-I signaling; Duck plague virus (DPV); ICP27; IFN-β; Innate immunity evasion.

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