Journal Article

Interferon-stimulated TRIM69 interrupts dengue virus replication by ubiquitinating viral nonstructural protein 3

Zou, Chunling, Wang, Xiujuan, Pan, Wen, Wu, Qihan, Wang, Penghua, Wang, Kezhen, Dai, Jianfeng, Huang, Chenxiao, Feng, Tingting

2018

Overview

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 polyubiquitination and degradation. Finally, Lys104 of NS3 is identified as the target of TRIM69-mediated ubiquitination. Our study demonstrates that TRIM69 restricts DENV replication by specifically ubiquitinating a viral nonstructural protein.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: A549 Cells / Animals / Anopheles / Antiviral activity / Apoptosis / Biology / Biology and Life Sciences / Cells, Cultured / Dengue / Dengue fever / Dengue Virus - physiology / Diabetes / Gene Expression Regulation - drug effects / Genetic aspects / HEK293 Cells / HeLa Cells / Human Umbilical Vein Endothelial Cells / Humans / Immunology / In vivo methods and tests / Infections / Interferon / Interferon Type I - pharmacology / Laboratories / Medicine and Health Sciences / Mice / Mosquitoes / Protein Processing, Post-Translational - drug effects / Protein Processing, Post-Translational - genetics / Proteins / Replication / Research and analysis methods / Risk factors / RNA Helicases - metabolism / RNA polymerase / Serine Endopeptidases - metabolism / Target recognition / Tripartite Motif Proteins - drug effects / Tripartite Motif Proteins - genetics / Tripartite Motif Proteins - physiology / Tropical diseases / Ubiquitin / Ubiquitin-protein ligase / Ubiquitin-Protein Ligases - drug effects / Ubiquitin-Protein Ligases - genetics / Ubiquitin-Protein Ligases - physiology / Ubiquitination / Ubiquitination - drug effects / Ubiquitination - genetics / Up-Regulation - drug effects / Up-Regulation - genetics / Vector-borne diseases / Viral diseases / Viral Nonstructural Proteins - metabolism / Viral proteins / Virology / Virus replication / Virus Replication - drug effects / Virus Replication - genetics / Viruses