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

PLoS Pathogens

Xiujuan Wang¹  Kezhen Wang²  Chunling Zou³  Chenxiao Huang⁴ 

[1]Department Immunology, School of Medicine, the University of Connecticut Health Center, Farmington, Connecticut, United States of America

[2]Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, P. R. China

[3]Key Laboratory of Reproduction Regulation of NPFPC, SIPPR, IRD, Fudan University, Shanghai Institute of Planned Parenthood Research, Shanghai, P. R. China

[4]National Institute of Allergy and Infectious Diseases, UNITED STATES

DOI  :  10.1371/journal.ppat.1007287

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY