On June 22, 2021, Professor Du Yuzhen of Zhejiang University School of Medicine, Zhejiang Medical Second Hospital, and Professor Sun Ren of the University of Hong Kong jointly published the latest research results in the internationally renowned journal Cell Reports, reporting that the atypical kinase Riok3 activates viral infections.
Hongkong The paper is titled "Riok3 Inhibits the Antiviral Immune Response by Facilitating TRIM40-mediated RIG-I and MDA5 Degradation".
The activation of type I interferon signaling pathway is a key event for the body's natural immunity to respond to the invasion of foreign pathogens
The kinase Riok3 belongs to the RIO family and is conservatively expressed in higher eukaryotes
First, the author used genetic recombination to construct a myeloid cell line specifically knockout Riok3 transgenic mice, and used a variety of viruses to infect the Riok3 specific knockout macrophages extracted from mice, and found that the deletion of Riok3 selectively inhibits RNA The replication of viruses, but cannot inhibit the replication of DNA viruses
Genetically modified Subsequently, the authors used a variety of DNA/RNA chemical mimics to stimulate Riok3 knockout or knockdown primary cells, and found that Riok3 only has a negative regulatory effect on downstream pathways activated by RNA mimics recognized by RIG-I/MDA5.
In terms of mechanism research, the author used endogenous IP to confirm that Riok3 can bind to and promote the ubiquitination and protein degradation of RIG-I and MDA5, respectively
Finally, the authors used the myeloid cell line Riok3 specific knockout mouse model to confirm that Riok3-deficient mice can significantly inhibit the replication of RNA viruses in the body, thereby reducing deaths caused by infection
Related paper information: https://doi.
https://doi.
org/10.
1016/j.
celrep.
2021.
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org/10.
1016/j.
celrep.
2021.
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