Host protein Cyclophilin A regulates the natural immunity of antivirals mediated by RIG-I.

On June 8, Liu Wenjun of the Institute of Microbiology of the Chinese Academy of Sciences published a new study published online in the international journal life entitled Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral i responses, revealing the regulatory mechanism of host protein Cyclophilin A (Cyp A) to RIG-I-mediated antiviral natural immunity.
The study reveals how CypA affects virus replication by regulating natural immune response from the perspective of natural immunity, and for the first time sheds light on the role of CypA in rig-I-mediated natural immune signaling paths and its generalized regulatory mechanisms, and provides a deeper understanding of CypA's function in the field of antiviral natural immunity.
CypA is a peptide-based proline anti-isomerase that is widely present and highly conservative in a variety of tissues.
CypA is an in-cell recepposor of the immunosuppressant cyclosporin A (CsA) and plays an important role in protein folding, signal transdation, inflammation, tumor occurrence, and virus replication, but the role and regulatory mechanism of CypA in the natural immune process is not clear. The
team conducted a series of studies around CypA in the early stages, and found that CypA interacted with the M1 protein of influenza A virus, inhibited influenza virus replication by accelerating the ubiquitinization degradation of M1 protein, and significantly increased the resistance of genetically modified mice that over-expressed CypA to influenza viruses (Cellular Microbiology, 2009, 11 (5): 730-741; PloS ONE, 2012, 7 (2): e31063; Reports, 6,28978).
study further reveals how CypA affects virus replication by regulating the production of type I interferon from the perspective of natural immunity.
Experiments on 293T, BMDM, U937, human mononucleocytes, and mice showed that CypA inhibited the replication of RIG-I identification viruses such as SeV and VSV, promoted the production of type I interferon and interferon-induced genes activated by viral infection or poly (I:C) transflection, and significantly reduced the resistance of genes to viruses in mice.
SeV infection, CypA promotes the formation of phosphate and dicetalics of IRF3, and increases the phosphorylation of p65, indicating that CypA regulates both NF-B and IRF3 signaling paths.
further research has found that CypA can interact with RIG-I to enhance the binding between RIG-I and E3 Ubigen cytoenzyme TRIM25, thereby promoting TRIM25-mediated RIG-I's K63 Ubigenization and recruiting more RIG-I to bind to MAVS on mitochondria.
other hand, CypA enhances the stability of MAVS by binding competitively with TRIM25 and MAVS to inhibit the Ubimatization of K48 of TRIM25-mediated MAVS.
results show that CypA can promote the Ubigenization of RIG-I and inhibit the Ubigenization of K48 of MAVS, thus regulating the production of type I interferon.
model of CypA's regulatory mechanism for RIG-I-mediated antiviral natural immunity.
the C-side combination of CypA and RIG-I promotes the N-end combination of TRIM25 and RIG-I, enhancing the K63 ubimatization of RIG-I, and CypA and TRIM25 are competitively combined with MAVS to inhibit the K48 generalization of MAVS.
, associate researcher, and Liu Wenjun, a researcher, are the authors of the paper, and Liu Wei, a doctoral student, and Li Jing, an assistant researcher, are the first authors of the paper.
the research was funded by the National Natural Science Foundation of China (31472178, 31672531, 81621091) and the Key Research and Development Project of the Chinese Academy of Sciences (KSZD-EW-Z-005-001).
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