African swine fever virus pB475L evades host antiviral innate immunity via targeting STAT2 to inhibit IFN-I signaling.

Autor:	Huang Z; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Mai Z; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Kong C; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China., You J; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Lin S; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Gao C; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Zhang W; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Chen X; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China., Xie Q; College of Animal Science, South China Agricultural University, Guangzhou, China., Wang H; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, China., Tang S; Guangdong Provincial Key Laboratory of Utilization and Conservation of Food and Medicinal Resources in Northern Region, Shaoguan University, Shaoguan, China., Zhou P; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China. Electronic address: zhoupei@scau.edu.cn., Gong L; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; African Swine Fever Regional Laboratory of China, South China Agricultural University, Guangzhou, China. Electronic address: gonglang@scau.edu.cn., Zhang G; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China; Research Center for African Swine Fever Prevention and Control, South China Agricultural University, Guangzhou, China; Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture and Rural Affairs, Guangzhou, China. Electronic address: guihongzh@scau.edu.cn.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Jul; Vol. 300 (7), pp. 107472. Date of Electronic Publication: 2024 Jun 13.
DOI:	10.1016/j.jbc.2024.107472
Abstrakt:	African swine fever virus (ASFV) causes severe disease in domestic pigs and wild boars, seriously threatening the development of the global pig industry. Type I interferon (IFN-I) is an important component of innate immunity, inducing the transcription and expression of antiviral cytokines by activating Janus-activated kinase-signal transducer and activator of transcription (STAT). However, the underlying molecular mechanisms by which ASFV antagonizes IFN-I signaling have not been fully elucidated. Therefore, using coimmunoprecipitation, confocal microscopy, and dual luciferase reporter assay methods, we investigated these mechanisms and identified a novel ASFV immunosuppressive protein, pB475L, which interacts with the C-terminal domain of STAT2. Consequently, pB475L inhibited IFN-I signaling by inhibiting STAT1 and STAT2 heterodimerization and nuclear translocation. Furthermore, we constructed an ASFV-B475L 7PM mutant strain by homologous recombination, finding that ASFV-B475L 7PM attenuated the inhibitory effects on IFN-I signaling compared to ASFV-WT. In summary, this study reveals a new mechanism by which ASFV impairs host innate immunity. Competing Interests: Conflict of interest The research was conducted without commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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