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African Swine Fever Virus MGF505-7R Interacts with Interferon Regulatory Factor 9 to Evade the Type I Interferon Signaling Pathway and Promote Viral Replication.
Huang, Zhao; Cao, Haoxuan; Zeng, Fanliang; Lin, Sizhan; Chen, Jianglin; Luo, Yi; You, Jianyi; Kong, Cuiying; Mai, Zhanzhuo; Deng, Jie; Guo, Weiting; Chen, Xiongnan; Wang, Heng; Zhou, Pei; Zhang, Guihong; Gong, Lang.
Afiliación
  • Huang Z; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Cao H; Henry Fok School of Biology and Agriculture, Shaoguan University, Shaoguan, China.
  • Zeng F; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
  • Lin S; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Chen J; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
  • Luo Y; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • You J; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
  • Kong C; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Mai Z; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
  • Deng J; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Guo W; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, 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.
  • Wang H; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
  • Zhou P; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Zhang G; Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
  • Gong L; African Swine Fever Regional Laboratory of China (Guangzhou), Guangzhou, China.
J Virol ; 97(3): e0197722, 2023 03 30.
Article en En | MEDLINE | ID: mdl-36815839
African swine fever (ASF) is an acute and severe infectious disease caused by the ASF virus (ASFV). The mortality rate of ASF in pigs can reach 100%, causing huge economic losses to the pig industry. Here, we found that ASFV protein MGF505-7R inhibited the beta interferon (IFN-ß)-mediated Janus-activated kinase-signal transducer and activation of transcription (JAK-STAT) signaling. Our results demonstrate that MGF505-7R inhibited interferon-stimulated gene factor 3 (ISGF3)-mediated IFN-stimulated response element (ISRE) promoter activity. Importantly, we observed that MGF505-7R inhibits ISGF3 heterotrimer formation by interacting with interferon regulatory factor 9 (IRF9) and inhibits the nuclear translocation of ISGF3. Moreover, to demonstrate the role of MGF505-7R in IFN-I signal transduction during ASFV infection, we constructed and evaluated ASFV-ΔMGF505-7R recombinant viruses. ASFV-ΔMGF505-7R restored STAT2 and STAT1 phosphorylation, alleviated the inhibition of ISGF3 nuclear translocation, and showed increased susceptibility to IFN-ß, unlike the parental GZ201801 strain. In conclusion, our study shows that ASFV protein MGF505-7R plays a key role in evading IFN-I-mediated innate immunity, revealing a new mode of evasion for ASFV. IMPORTANCE ASF, caused by ASFV, is currently prevalent in Eurasia, with mortality rates reaching 100% in pigs. At present, there are no safe or effective vaccines against ASFV. In this study, we found that the ASFV protein MGF505-7R hinders IFN-ß signaling by interacting with IRF9 and inhibiting the formation of ISGF3 heterotrimers. Of note, we demonstrated that MGF505-7R plays a role in the immune evasion of ASFV in infected hosts and that recombinant viruses alleviated the effect on type I IFN (IFN-I) signaling and exhibited increased susceptibility to IFN-ß. This study provides a theoretical basis for developing vaccines against ASFV using strains with MGF505-7R gene deletions.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / Interferón Tipo I / Fiebre Porcina Africana / Virus de la Fiebre Porcina Africana / Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón Límite: Animals Idioma: En Revista: J Virol Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Replicación Viral / Interferón Tipo I / Fiebre Porcina Africana / Virus de la Fiebre Porcina Africana / Subunidad gamma del Factor 3 de Genes Estimulados por el Interferón Límite: Animals Idioma: En Revista: J Virol Año: 2023 Tipo del documento: Article País de afiliación: China