Prof. Gao Chengjiang's Group Discovered a Novel Regulatory Mechanism of Innate Antiviral Immunity
Source：Gao Chengjiang
2016-12-06
Recently, Prof. Chengjiang Gao (Department of Immunology, the School of Basic Medical Sciences, Shandong University) has published a paper in Nature Immunology about the regulation of innate antiviral immunity by the E3 ubiquitin ligase RNF128 (Song G. et al, E3 Ubiquitin Ligase RNF128 Promotes Innate Antiviral Immunity Through K63-Linked Ubiquitination of TBK1. Nat Immunol. 2016 Dec;17(12):1342-1351.).
Innate immunity is the first line of host defense against microbial invasion. Activation of the innate immune response requires pattern recognition receptors (PRRs) recognition of pathogen-associated molecular patterns (PAMPs). Upon recognition of the nucleic acids, these PRRs recruit different adaptors to activate expression of type I IFN, pro-inflammatory cytokines and other downstream antiviral proteins, which is critical for eliciting immediate antiviral responses to eradicate virus infection. In order to eliminate virus infection efficiently, at the same time, to prevent the tissue damage of the host, activation of innate immunity must be tightly regulated to maintain immune homeostasis. But, how the activation of innate antiviral immunity is regulated remains elusive.
In this paper, the authors identified a novel positive regulator RNF128, which targets the essential molecule TBK1 in the innate antiviral signaling pathway. They found that that virus infection could induce RNF128 expression. As an E3 ligase, RNF128 was found to directly interact with TBK1 and catalyze the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, and IFN-β production. Deficiency of RNF128 expression attenuated IFN-β production and innate antiviral immune responses in vitro and in vivo to both RNA virus and DNA virus. Therefore, this study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.
Ph.D. student Song Guanhua from SDU is the first authors of this paper. Prof. Gao Chengjiang from the School of Basic Medical Sciences of SDU is the corresponding author. This work was supported by grants from the Natural Science Foundation of China.
Innate immunity is the first line of host defense against microbial invasion. Activation of the innate immune response requires pattern recognition receptors (PRRs) recognition of pathogen-associated molecular patterns (PAMPs). Upon recognition of the nucleic acids, these PRRs recruit different adaptors to activate expression of type I IFN, pro-inflammatory cytokines and other downstream antiviral proteins, which is critical for eliciting immediate antiviral responses to eradicate virus infection. In order to eliminate virus infection efficiently, at the same time, to prevent the tissue damage of the host, activation of innate immunity must be tightly regulated to maintain immune homeostasis. But, how the activation of innate antiviral immunity is regulated remains elusive.
In this paper, the authors identified a novel positive regulator RNF128, which targets the essential molecule TBK1 in the innate antiviral signaling pathway. They found that that virus infection could induce RNF128 expression. As an E3 ligase, RNF128 was found to directly interact with TBK1 and catalyze the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, and IFN-β production. Deficiency of RNF128 expression attenuated IFN-β production and innate antiviral immune responses in vitro and in vivo to both RNA virus and DNA virus. Therefore, this study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.
Ph.D. student Song Guanhua from SDU is the first authors of this paper. Prof. Gao Chengjiang from the School of Basic Medical Sciences of SDU is the corresponding author. This work was supported by grants from the Natural Science Foundation of China.
