GPATCH3 negatively regulates the natural immune signaling path paths mediated by RIG-I-like subjects.

Recently, the research team of Wang Yanxuan of Wuhan Virus Research Institute of the Chinese Academy of Sciences made new progress in antiviral natural immunity.
the team found that GPATCH3 inhibits the formation of downstream signal complexes and negatively regulates the natural immune signaling path paths mediated by RIG-I-like subjects.
paper GPATCH3 negatively regulates RLR-mediated innate antiviral responses by disrupting the assembly of VISA signalosome published online in the journal PLOS Pathogens.
pattern recognition receptors (PRRs) are the host's first barrier against pathogenic microorganisms and play an important role in the natural immunity of cells against viruses.
RIG-I and melanoma differentiation gene 5 (melanoma differentiation-associated gene 5, MDA5) is a member of the RIG-I receptor (RIG-I receptors, RLRs) family that identifies RNA released by the virus into the plasma and induces the production of type I interferon and inflammatory factors through a series of signaling cascades to build an antiviral immune response.
the formation of the connector protein VISA signalosome is necessary for the activation of the signaling path in the RIG-I-like sensor-mediated signaling path.
previous studies, Wang Yanxuan found that WDR5 promotes the assembly and stability of VISA signal complexes and regulates the natural immune signaling path path path of RIG-I-like subject mediated.
the study, Wang's team screened cDNA expression clones and found another important regulator in antiviral natural immunity, GPATCH3 (G-patch domain containing protein).
Overexpression of GPATCH3 in cells inhibits the activation of IFN-b-reported genes induced by RNA virus SeV, while the expression of GPATCH3 is reduced, and transcription of IFN-B1 and its downstream genes induced by RNA viruses is significantly enhanced (Figure 1).
and when the expression level of GPATCH3 decreased, replication of SeV and VSV was significantly inhibited, indicating that GPATCH3 inhibited the antiviral immune response of cells (Figure 2).
, the researchers used CRISPR-Cas9 technology to build the GPATCH3 gene to knock out cells.
Compared with wild cells, after RNA virus infection, the transcription of the GPATCH3 gene knock-out cell IFNB1 gene was significantly enhanced, and after GPATCH3 knock-out cells complemented GPATCH3, the transcription level of the RNA virus-induced IFNB1 gene was similar to that of wild cells, further indicating that GPATCH3 can negatively regulate the natural immune signaling path of RIG-I-like mediated.
GPATCH3 mechanism study shows that the virus can induce GPATCH3 to interact with VISA located in mitochondrials, prevent the formation of VISA complex (VISA/TRAF6/TBK1) (Figure 3), inhibit the rig-I receptor-mediated natural immune signaling path, and help the virus immune escape.
the study found another important regulatory factor in the natural immune response of cells against the virus, GPATCH3.
through a series of GPATCH3 knock-down/knock-out and over-expression experiments, it is proved that GPATCH3 can negatively regulate the Immune signaling path of RIG-I-mediated, inhibiting the antiviral immune response of cells.
the study also revealed that GPATCH3 helps people to better understand the regulatory pathways of antiviral natural immune signaling by hindering the formation of negative regulatory mechanisms in VISA complexes.
, a researcher at the Wuhan Virus Institute, is the author of the thesis newsletter and the first author of the doctoral student.
the study was supported by the National Science Foundation for Distinguished Young People (31425010), the National Natural Science Foundation of China (31321001), the Ministry of Science and Technology of China (2014cb542603, 2015cb554302) and the Chinese Academy of Sciences.
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