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The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.
Zeng, Yan; Xu, Shuai; Wei, Yanli; Zhang, Xuegang; Wang, Qian; Jia, Yane; Wang, Wanbing; Han, Lu; Chen, Zhaoshan; Wang, Zhengxiang; Zhang, Bo; Chen, Hualan; Lei, Cao-Qi; Zhu, Qiyun.
Afiliação
  • Zeng Y; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Xu S; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Wei Y; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Zhang X; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Wang Q; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Jia Y; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Wang W; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Han L; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Chen Z; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Wang Z; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
  • Zhang B; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
  • Chen H; State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
  • Lei CQ; Hubei Key Laboratory of Cell Homeostasis, Frontier Science Center for Immunology and Metabolism, State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
  • Zhu Q; State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
PLoS Pathog ; 17(2): e1009300, 2021 02.
Article em En | MEDLINE | ID: mdl-33577621
ABSTRACT
Influenza A virus (IAV) has evolved various strategies to counteract the innate immune response using different viral proteins. However, the mechanism is not fully elucidated. In this study, we identified the PB1 protein of H7N9 virus as a new negative regulator of virus- or poly(IC)-stimulated IFN induction and specifically interacted with and destabilized MAVS. A subsequent study revealed that PB1 promoted E3 ligase RNF5 to catalyze K27-linked polyubiquitination of MAVS at Lys362 and Lys461. Moreover, we found that PB1 preferentially associated with a selective autophagic receptor neighbor of BRCA1 (NBR1) that recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation. The degradation cascade mediated by PB1 facilitates H7N9 virus infection by blocking the RIG-I-MAVS-mediated innate signaling pathway. Taken together, these data uncover a negative regulatory mechanism involving the PB1-RNF5-MAVS-NBR1 axis and provide insights into an evasion strategy employed by influenza virus that involves selective autophagy and innate signaling pathways.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Proteínas Virais / Ubiquitina-Proteína Ligases / Peptídeos e Proteínas de Sinalização Intracelular / Proteínas Adaptadoras de Transdução de Sinal / Proteínas de Ligação a DNA / Influenza Humana / Imunidade Inata Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Autofagia / Proteínas Virais / Ubiquitina-Proteína Ligases / Peptídeos e Proteínas de Sinalização Intracelular / Proteínas Adaptadoras de Transdução de Sinal / Proteínas de Ligação a DNA / Influenza Humana / Imunidade Inata Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: PLoS Pathog Ano de publicação: 2021 Tipo de documento: Article País de afiliação: China