E3 ubiquitin ligase TRIM21 restricts hepatitis B virus replication by targeting HBx for proteasomal degradation.

Antiviral Research
Yahui SongWei Xu

Abstract

As a cytosol ubiquitin ligase and antibody receptor, Tripartite motif-containing 21 (TRIM21) has been reported to mediate the restriction of hepatitis B virus (HBV) through an HBx-antibody-dependent intracellular neutralization (ADIN) mechanism. However, whether TRIM21 limits HBV replication by targeting viral proteins remains unclarified. In this study, we demonstrate that TRIM21 inhibits HBV gene transcription and replication in HBV plasmid transfected and HBV-infected hepatoma cells. RING and PRY-SPRY domains are involved in this activity. TRIM21 interacts with HBx protein and targets HBx for ubiquitination and proteasomal degradation, leading to impaired HBx-mediated degradation of structural maintenance of chromosomes 6 (Smc6) and suppression of HBV replication. TRIM21 fails to restrict the replication of an HBx-deficient HBV. And knock-down of Smc6 largely impairs the anti-HBV activity of TRIM21 in HepG2 cells. In a hydrodynamic injection (HDI)-based HBV mouse model, we confirm an in vivo anti-HBV and anti-HBx therapeutic effect of TRIM21 by over-expression or knocking-out strategy. Our findings reveal a novel mechanism that TRIM21 restricts HBV replication through targeting HBx-Smc5/6 pathway, which may have an implicati...Continue Reading

References

May 1, 1988·The Journal of Experimental Medicine·E Ben-ChetritE M Tan
Jul 17, 2007·Clinical Microbiology Reviews·Alexandra Valsamakis
Jul 22, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rowan HiggsCaroline A Jefferies
Mar 7, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kai YangChen Wang
Jun 26, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jiejie XuJianxin Gu
Aug 3, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Bassem S S GuirgisHassan M E Azzazy
Dec 18, 2013·Journal of Molecular Biology·Ricardo RajsbaumGijs A Versteeg
Aug 26, 2014·Nature Reviews. Molecular Cell Biology·Kristian JeppssonCamilla Sjögren
Feb 17, 2015·Cellular & Molecular Immunology·Chen YangBing Sun
Jul 29, 2015·Journal of Hepatology·Souphalone LuangsayFabien Zoulim
Jan 19, 2016·Antiviral Research·Wenchun FanXiangmin Li
Mar 18, 2016·Autophagy·Tomonori KimuraVojo Deretic
Sep 15, 2016·Cell Reports·Christopher M MurphyLishan Su
Feb 27, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Wen ZhangZhenghong Yuan
Jul 1, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaoming ChengT Jake Liang
Sep 6, 2017·Nature Microbiology·Konstantin M J SparrerMichaela U Gack
Mar 2, 2018·Genes·Luis SendraSalvador F Aliño
Mar 11, 2018·Cellular & Molecular Immunology·Fengchao XuGuangyun Tan
Jun 24, 2018·Epigenetics & Chromatin·Kai O HenselJan Postberg
Aug 24, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gaetan LigatThomas F Baumert
Oct 31, 2018·Molecular Pharmaceutics·Xiaodan CaiZigang Li
Feb 2, 2019·Journal of Viral Hepatitis·Fengping JiaoFengmin Lu
Jun 7, 2019·Journal of Virology·Dmytro KornyeyevRudolf K Beran
Aug 14, 2019·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Yuanyuan YangSidong Xiong

❮ Previous
Next ❯

Citations

Sep 25, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Masataka Tsuge

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

© 2021 Meta ULC. All rights reserved