2. Academic Validation
  3. African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation

African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation

  • Viruses. 2021 Oct 11;13(10):2046. doi: 10.3390/v13102046.
Xueliang Liu 1 2 3 4,  Da Ao 1 2 3 4,  Sen Jiang 1 2 3 4,  Nengwen Xia 1 2 3 4,  Yulin Xu 1 2 3 4,  Qi Shao 1 2 3 4,  Jia Luo 1 2 3 4,  Heng Wang 1 2 4,  Wanglong Zheng 1 2 3 4,  Nanhua Chen 1 2 3 4,  François Meurens 5 6,  Jianzhong Zhu 1 2 3 4
Affiliations

Affiliations

  • 1 College Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
  • 2 Comparative Medicine Research Institute, Yangzhou University, Yangzhou 225009, China.
  • 3 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Yangzhou 225009, China.
  • 4 Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China.
  • 5 BIOEPAR, INRAE, Oniris, 44307 Nantes, France.
  • 6 Department of Veterinary Microbiology and Immunology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E2, Canada.
PMID: 34696476 DOI: 10.3390/v13102046
Abstract

African swine fever (ASF) is mainly an acute hemorrhagic disease which is highly contagious and lethal to domestic pigs and wild boars. The global pig industry has suffered significant economic losses due to the lack of an effective vaccine and treatment. The African swine fever virus (ASFV) has a large genome of 170-190 kb, encoding more than 150 proteins. During Infection, ASFV evades host innate immunity via multiple Viral Proteins. A528R is a very important member of the polygene family of ASFV, which was shown to inhibit IFN-β production by targeting NF-κB, but its mechanism is not clear. This study has shown that A528R can suppress the TLR8-NF-κB signaling pathway, including the inhibition of downstream promoter activity, NF-κB p65 phosphorylation and nuclear translocation, and the Antiviral and Antibacterial activity. Further, we found the cellular co-localization and interaction between A528R and p65, and ANK repeat domains of A528R and RHD of p65 are involved in their interaction and the inhibition of p65 activity. Therefore, we conclude that A528R inhibits TLR8-NF-κB signaling by targeting p65 activation and nuclear translocation.

Keywords

A528R protein; African swine fever virus; NF-κB; TLR8; p65.

Figures
Products