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Scientists Find a Negative Regulator of Innate Antiviral Immune Responses

May 11, 2017     Email"> PrintText Size

Recognition of conserved molecular structures of viruses by the host pattern-recognition receptors (PRRs) initiates innate antiviral immune responses. Several families of PRRs, including Toll-like receptors (TLRs), RIG-like receptors (RLRs), NOD-like receptors (NLRs) and recently identified DNA sensors, have been shown to sense different microbial components. 

Previously, the research group led by Prof. WANG Yanyi from Wuhan Institute of Virology of the Chinese Academy of Sciences identified VISA (also named as MAVS, IPS-1 and Cardif) as a critical adaptor of virus-triggered, RLR-mediated induction of innate antiviral responses.  

In the present study, the scientists further found that GPATCH3, a functionally uncharacterized protein, interacted with mitochondria-localized VISA upon virus infection and disrupted the assembly of VISA-signalosome.  

They reveal that GPATCH3 acts as a negative regulator of VISA and functions as a brake of RLR-mediated antiviral innate responses. Knockdown of GPATCH3 significantly enhanced SeV-triggered induction of downstream antiviral genes in multiple cell lines, including primary PBMCs and HFFs but had no marked effects on TLR3- or DNA sensor-mediated signaling.  

GPATCH3-deficient cells showed higher induction of IFNB1 compared with wild-type cells upon SeV or VSV infection. Mechanistically, GPATCH3 interacted with VISA and impaired assembly of the VISA-associated signaling complexes. This discovery helps to understand how the innate antiviral responses are delicately regulated.  

The results have been published in PLoS Pathogens entitled "GPATCH3 negatively regulates RLR-mediated innate antiviral responses by disrupting the assembly of VISA signalosome".  

This work was supported by National Science Fund for Distinguished Young Scholars, the National Nature Science Fundation of China, Ministry of Science and Technology and the Key Program of the Chinese Academy of Sciences. 

 

GPATCH3 interrupts assembly of the VISA-associated signaling complexes. (Image by WANG Yanyi) 

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(Editor: ZHANG Nannan)

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WANG Yanyi

Wuhan Institute of Virology

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E-mail: wangyy@wh.iov.cn

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