238 Innate immune response triggered by influenza A virus is negatively regulated by suppressor of cytokine signaling (SOCS)1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway

Cytokine ◽  
2008 ◽  
Vol 43 (3) ◽  
pp. 296
Author(s):  
Julien Pothlichet ◽  
Michel Chignard ◽  
Mustapha Si-Tahar
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Innate Immune Response ◽  
Influenza A ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Dependent Pathway

scholarly journals The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation

2021 ◽  
Vol 17 (2) ◽  
pp. e1009300
Author(s):  
Yan Zeng ◽  
Shuai Xu ◽  
Yanli Wei ◽  
Xuegang Zhang ◽  
Qian Wang ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza A Virus ◽  
Innate Immune Response ◽  
Influenza A ◽  
Innate Immune ◽  
Negative Regulator ◽  
Poly I:C ◽  
H7n9 Virus ◽  
Autophagic Degradation ◽  
Negative Regulatory Mechanism

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.

scholarly journals Influenza A virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1

2020 ◽  
Author(s):  
Yinping Du ◽  
Fan Yang ◽  
Qiuxia Wang ◽  
Nuo Xu ◽  
Yizhang Xie ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Innate Immune ◽  
Cytokine Signaling ◽  
Type I ◽  
Type Ii ◽  
Innate Immune Responses ◽  
Suppressor Of Cytokine Signaling ◽  
Interferon Responses ◽  
Socs Protein

Abstract BACKGROUND Although influenza A virus (IAV) employs diverse strategies to evade IFN responses by inhibiting the synthesis of IFN, how IAV regulates signaling downstream of IFN is incompletely understood. METHODS In this study, we used Western blot-based protein analysis coupled with RT-qPCR, overexpression and RNA interference to investigate the regulation of JAK1 by IAV infection. RESULTS The results indicated that JAK1 was ubiquitinated and degraded, resulting in inhibition of type I and type II IFN responses, demonstrating that IAV antagonizes the IFN-activated JAK/STAT signaling pathway by inducing the degradation of JAK1. Furthermore. IAV infection upregulated the suppressor of cytokine signaling (SOCS) protein SOCS1, and SOCS1 mediated the ubiquitination and degradation of JAK1. CONCLUSION: Collectively, our findings suggest that IAV infection induced SOCS1 expression promotes JAK1 degradation, which in turn inhibits host innate immune responses.

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