Year: 2019
Type: article
Abstract: To understand the molecular mechanisms that mediate the anti-hepatitis B virus (HBV) effect of interferon (IFN) therapy, we conduct high-throughput bimolecular fluorescence complementation screening to identify potential physical interactions between the HBx protein and 145 IFN-stimulated genes (ISGs). Seven HBx-interacting ISGs have consistent and significant inhibitory effects on HBV replication, among which TRIM5γ suppresses HBV replication by promoting K48-linked ubiquitination and degradation of the HBx protein on the K95 ubiquitin site. The B-Box domain of TRIM5γ under overexpression conditions is sufficient to trigger HBx degradation and is responsible both for interacting with HBx and recruiting TRIM31, which is an ubiquitin ligase that triggers HBx ubiquitination. High expression levels of TRIM5γ in IFN-α-treated HBV patients might indicate a better therapeutic effect. Thus, our studies identify a crucial role for TRIM5γ and TRIM31 in promoting HBx degradation, which may facilitate the development of therapeutic agents for the treatment of patients with IFN-resistant HBV infection.
Source: Cell Reports
Institutions: First Hospital of Jilin University, Chinese Academy of Sciences, Institute of Biophysics, University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, University of California, Los Angeles, Jilin University, Chinese Academy of Medical Sciences & Peking Union Medical College, Suzhou Institute of Systems Medicine, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China, Fudan University, People's Government of Jilin Province, Jilin University, Natural Science Foundation of Jiangsu Province, Jiangsu Science and Technology Department, Sichuan Provincial Youth Science and Technology Fund, Education Department of Jilin Province, Innovative Medicines Initiative, National Institutes of Health, First Hospital of Jilin University, Chinese Academy of Medical Sciences Initiative for Innovative Medicine, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W2995216587