2. Academic Validation
  3. African swine fever virus A137R protein inhibits NF-κB activation via suppression of MyD88 signaling in PK15 and 3D4/21 cells in vitro

African swine fever virus A137R protein inhibits NF-κB activation via suppression of MyD88 signaling in PK15 and 3D4/21 cells in vitro

  • Vet Microbiol. 2024 May:292:110067. doi: 10.1016/j.vetmic.2024.110067.
Yang Xu 1,  Lei Wu 1,  Jinxuan Hong 2,  Xiaojuan Chi 3,  Meichun Zheng 3,  Liwei Wang 3,  Ji-Long Chen 4,  Guijie Guo 5
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China; Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
  • 2 Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
  • 3 Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China.
  • 4 Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China; Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China. Electronic address: chenjilong@fafu.edu.cn.
  • 5 Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China; Key Laboratory of Fujian-Taiwan Animal Pathogen Biology, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou, China. Electronic address: guojie1125@163.com.
PMID: 38564905 DOI: 10.1016/j.vetmic.2024.110067
Abstract

African swine fever (ASF) is an infectious disease with high mortality caused by African swine fever virus (ASFV), which poses a great threat to the global swine industry. ASFV has evolved multiple strategies to evade host Antiviral innate immunity by perturbing inflammatory responses and interferon production. However, the molecular mechanisms underlying manipulation of inflammatory responses by ASFV proteins are not fully understood. Here, we report that A137R protein of ASFV is a key suppressor of host inflammatory responses. Ectopic expression of ASFV A137R in HEK293T cells significantly inhibited the activation of IL-8 and NF-κB promoters triggered by Sendai virus (SeV), influenza A virus (IAV), or vesicular stomatitis virus (VSV). Accordingly, forced A137R expression caused a significant decrease in the production of several inflammatory cytokines such as IL-8, IL-6 and TNF-α in the cells infected with SeV or IAV. Similar results were obtained from experiments using A137R overexpressing PK15 and 3D4/21 cells infected with SeV or VSV. Furthermore, we observed that A137R impaired the activation of MAPK and NF-κB signaling pathways, as enhanced expression of A137R significantly decreased the phosphorylation of JNK, p38 and p65 respectively upon viral Infection (SeV or IAV) and IL-1β treatment. Mechanistically, we found that A137R interacted with MyD88, and dampened MyD88-mediated activation of MAPK and NF-κB signaling. Together, these findings uncover a critical role of A137R in restraining host inflammatory responses, and improve our understanding of complicated mechanisms whereby ASFV evades innate immunity.

Keywords

A137R; ASFV; Inflammatory response; MyD88; NF-κB.

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