On Aug 26, 2018, researchers at Dr. Dai’s group published an article entitled “Interferon-Stimulated TRIM69 Interrupts Dengue Virus replication by ubiquitinating Viral Nonstructural Protein 3” in PLoS Pathogens. http://www.plospathogens.org/article/related/info:doi/10.1371/journal.ppat.1007287
Mosquito-borne viruses, such as Dengue virus (DENV) and Zika Virus (ZIKV), have become global threats to human health in recent years. In order to eliminate viral infections, hundreds of interferon-stimulated genes (ISGs) are induced via type I interferons (IFNs). However, the functions and mechanisms of most ISGs are largely unclear. A tripartite motif (TRIM) protein encoding gene TRIM69 is induced by dengue virus (DENV) infection as an ISG. TRIM69 restricts DENV replication, and its RING domain, which has the E3 ubiquitin ligase activity, is critical for its antiviral activity. An in vivo study further confirmed that TRIM69 contributes to the control of DENV infection in immunocompetent mice. Unlike many other TRIM family members, TRIM69 is not involved in modulation of IFN signaling. Instead，TRIM69 interacts with DENV Nonstructural Protein 3 (NS3) directly and mediates its K11-linked polyubiquitination and degradation. Finally, Lys104 of NS3 is identified as the target of TRIM69-mediated ubiquitination. This study demonstrates that TRIM69 restricts DENV replication by specifically ubiquitinating a viral nonstructural protein.
Kezhen Wang, Chunling Zou, and Xiujuan Wang are co-first authors. Chenxiao Huang, Tingting Feng, Wen Pan, ect. are contributing authors. Prof. Jianfeng Dai is the corresponding author. This work was supported by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT), National Natural Science Foundation of China (31500700，31770933, and 81471571), and Natural Science Foundation of Colleges in Jiangsu Province (17KJA310005).