African Swine Fever Virus A528R Inhibits TLR8 Mediated NF-κB Activity by Targeting p65 Activation and Nuclear Translocation
2021
Liu, Xueliang | Ao, Da | Jiang, Sen | Xia, Nengwen | Xu, Yulin | Shao, Qi | Luo, Jia | Wang, Heng | Zheng, Wanglong | Chen, Nanhua | Meurens, François | Zhu, Jianzhong | Yangzhou University | Comparative Medicine Research Institute ; Yangzhou University | Joint International Research Laboratory of Agriculture and Agri-Product Safety ; Partenaires INRAE | Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses | Biologie, Epidémiologie et analyse de risque en Santé Animale (BIOEPAR) ; École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | University of Saskatchewan [Saskatoon, Canada] (U of S) | The work was partly supported by the National Key Research and Development Program of China (2017YFD0502301), Jiangsu Provincial Key R&D plan (BE2020398), Jiangsu agricultural science and technology independent innovation fund project: CX(21)2035, National Natural Science Foundation of China: 31672523 and a project funded by the Priority Academic Program, Development of Jiangsu Higher Education Institutions (PAPD).
International audience
Afficher plus [+] Moins [-]anglais. 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.
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