On October 24, a research article entitled "E3 Ubiquitin Ligase RNF128 Promotes Innate Antiviral Immunity Through K63-Linked Ubiquitination of TBK1" was published onNature Immunology.Nature Immunologyis one of the top journals in the field of immunology with a five years average impact factor of 23.4. This work was mainly accomplished by Shandong University. The partial work of virus infection was performed in the Institute of Basic Medicine, Shandong Academy of Medical Sciences of Shandong Province. 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.

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.

Prof. Gao Chengjiang is the awardee of National Science Fund for Distinguished Young Scholars, Taishan Scholar of Shandong Province and the director for Key Laboratory of Infection and Immunity of Shandong Province. Prof. Gao Chengjiang's main research interest is illuminating the molecular regulatory mechanisms of the innate immune responses. He has published multiple research articles in prestigious international journals includingJournal of Experimental Medicine,PLOS Pathogens,Journal of ImmunologyandJournal of Virologyet al. The publication of this paper indicates that Prof. Gao's lab and SDU has reached advanced world level and become one of the internationally known research institutes in the field of innate antiviral immunity. This work was supported in part by grants from the Natural Science Foundation of China.

Link of the paper: http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3588.html

Source: the School of Basic Medical Sciences

Written by: Song Guanhua

Edited by: Xie Tingting