Zeng Y(1), Xu S(1), Wei Y(1), Zhang X(1), Wang Q(1), Jia Y(1), Wang W(1), Han L(1), Chen Z(1), Wang Z(1), Zhang B(2), Chen H(2), Lei CQ(3), Zhu Q(1). Author information:
(1)State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary
Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China.
(2)State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research
Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
(3)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.
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(I:C)-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.
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