Liu Wenjun, research group of Institute of Microbiology, Chinese Academy of Sciences, revealed that the host protein, cyclophil

On June 8, 2017, the international well-known journal e life published the latest research results of Liu Wenjun research group, Institute of Microbiology, Chinese Academy of Sciences, entitled "cyclin A-regulated ubiquitination is critical for rig-i-medicated antiviral immune responses", which revealed the host protein cyclin The regulatory mechanism of a (CyPA, cyclophilin A) on the natural immune system of anti-virus mediated by rig-i This study reveals how CyPA affects virus replication by regulating natural immune response from the perspective of natural immunity It is the first time to clarify the role of CyPA in the natural immune signaling pathway mediated by RIG-I and its ubiquitination regulation mechanism, and to further understand the function of CyPA in the field of antiviral natural immunity Liu Wei, doctoral candidate, Li Jing, assistant researcher, is the first author of the paper, and sun Lei, associate researcher, and Liu Wenjun, researcher, are the corresponding authors CyPA is a peptidylprolyl CIS trans isomerase, which is widely existed in various tissues and highly conserved CyPA is the intracellular receptor of immunosuppressant cyclosporin A (CSA), and plays an important role in protein folding, signal transduction, inflammation, tumorigenesis and virus replication However, the role and regulatory mechanism of CyPA in natural immune process are not clear In the early stage, the research group carried out a series of research work around CyPA, and found that CyPA interacted with M1 protein of influenza A virus, accelerated the ubiquitin degradation of M1 protein and inhibited the replication of influenza virus, and the anti influenza virus ability of transgenic mice overexpressing CyPA was significantly enhanced (cellular microbiology, 2009, 11 (5): 730-741; PLoS One, 2012, 7 (2): e31063; Scientific Report, 6, 28978)。 From the perspective of natural immunity, this study further reveals how CyPA affects virus replication by regulating the production of type I interferon The experimental results on 293T, bmdm, U937, human monocytes and mice showed that CyPA inhibited the replication of RIG-I recognized viruses such as sev and VSV, promoted the generation of virus infection or poly (I: C) transfected activated interferon I and interferon induced genes, and the antiviral ability of knockout mice was significantly reduced After sev infection, CyPA promoted the phosphorylation and dimer formation of IRF3, and upregulated the phosphorylation of p65, indicating that CyPA regulated both NF - κ B and IRF3 signaling pathways Further research shows that CyPA can interact with RIG-I, enhance the binding between RIG-I and E3 ubiquitin ligase trim25, so as to promote the k63 ubiquitination of RIG-I mediated by trim25, and recruit more RIG-I to bind to Mavs on mitochondria On the other hand, CyPA can inhibit K48 ubiquitination of Mavs mediated by trim25 and enhance the stability of Mavs by competitively combining with MAVs The above results show that CyPA can promote k63 ubiquitination of RIG-I and inhibit K48 ubiquitination of Mavs, thus positively regulate the production of type I interferon The regulatory mechanism of CyPA on the natural immune response to anti-virus mediated by rig-i CyPA and rim25 competitively combined with Mavs to inhibit the K48 ubiquitination of MAVs.