The Hepatitis B Virus Interactome: A Comprehensive Overview DOI Creative Commons
Ellen Van Damme,

Jolien Vanhove,

Bryan Severyn

et al.

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: Sept. 16, 2021

Despite the availability of a prophylactic vaccine, chronic hepatitis B (CHB) caused by virus (HBV) is major health problem affecting an estimated 292 million people globally. Current therapeutic goals are to achieve functional cure characterized HBsAg seroclearance and absence HBV-DNA after treatment cessation. However, at present, thought be complicated due presence covalently closed circular DNA (cccDNA) integrated HBV-DNA. Even if episomal cccDNA silenced or eliminated, it remains unclear how important high level that expressed from HBV for pathology. To identify therapies could bring about rates cure, in-depth knowledge virus’ biology imperative pinpoint mechanisms novel targets. The viral proteins considered integral control maintenance life cycle through direct interaction with host proteome they help create most optimal environment whilst avoiding immune detection. New HBV-host protein interactions continuously being identified. Unfortunately, compendium recent information lacking interactome unavailable. This article provides comprehensive review virus-host relationship entry release, as well cccDNA, HBc, HBx.

Language: Английский

Hepatitis B virus infection DOI
Man‐Fung Yuen, Ding‐Shinn Chen, Geoffrey Dusheiko

et al.

Nature Reviews Disease Primers, Journal Year: 2018, Volume and Issue: 4(1)

Published: June 6, 2018

Language: Английский

Citations

680
Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential DOI
Yuchen Xia, Haitao Guo

Antiviral Research, Journal Year: 2020, Volume and Issue: 180, P. 104824 - 104824

Published: May 22, 2020

Language: Английский

Citations

144
The Role of cccDNA in HBV Maintenance DOI Creative Commons
Lena Allweiss, Maura Dandri

Viruses, Journal Year: 2017, Volume and Issue: 9(6), P. 156 - 156

Published: June 21, 2017

Chronic hepatitis B virus (HBV) infection continues to be a major health burden worldwide; it can cause various degrees of liver damage and is strongly associated with the development cirrhosis hepatocellular carcinoma. The molecular mechanisms determining HBV persistence are not fully understood, but these appear multifactorial unique replication strategy employed by enables its maintenance in infected hepatocytes. Both stability genome, which forms stable minichromosome, covalently closed circular DNA (cccDNA) hepatocyte nucleus, inability immune system resolve chronic believed key chronicity. Since true cure requires clearance intranuclear cccDNA from hepatocytes, understanding involved biogenesis, regulation mandatory achieve eradication. This review will summarize state knowledge on including impact current treatments activity. We focus events challenging dividing

Language: Английский

Citations

169
The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation DOI Creative Commons
Quanxin Long, Ran Yan,

Jieli Hu

et al.

PLoS Pathogens, Journal Year: 2017, Volume and Issue: 13(12), P. e1006784 - e1006784

Published: Dec. 29, 2017

Hepadnavirus covalently closed circular (ccc) DNA is the bona fide viral transcription template, which plays a pivotal role in infection and persistence. Upon infection, non-replicative cccDNA converted from incoming de novo synthesized genomic relaxed (rc) DNA, presumably through employment of host cell's repair mechanisms nucleus. The conversion rcDNA into requires preparation extremities at nick/gap regions for strand ligation. After screening 107 cellular genes, we herein report that ligase (LIG) 1 3 play critical formation. Ligase inhibitors or functional knock down/out LIG1/3 significantly reduced production an vitro formation assay, cccDNA-producing cells without direct effect on core replication. In addition, transcomplementation corresponding knock-out knock-down was able to restore Furthermore, LIG4, component non-homologous end joining apparatus, found be responsible double stranded linear (dsl) but not rcDNA. conclusion, demonstrate hepadnaviruses utilize whole spectrum ligases formation, sheds light coherent molecular pathway biosynthesis, as well development novel antiviral strategies treatment hepatitis B.

Language: Английский

Citations

111
Targets and future direct-acting antiviral approaches to achieve hepatitis B virus cure DOI
Tarik Asselah, Dimitri Loureiro,

Nathalie Boyer

et al.

˜The œLancet. Gastroenterology & hepatology, Journal Year: 2019, Volume and Issue: 4(11), P. 883 - 892

Published: Oct. 7, 2019

Language: Английский

Citations

92
Interferon-inducible MX2 is a host restriction factor of hepatitis B virus replication DOI
Yongxiang Wang, Matthias Niklasch, Tiantian Liu

et al.

Journal of Hepatology, Journal Year: 2019, Volume and Issue: 72(5), P. 865 - 876

Published: Dec. 18, 2019

Language: Английский

Citations

88
Mechanism of Hepatitis B Virus cccDNA Formation DOI Creative Commons
Lei Wei, Alexander Ploß

Viruses, Journal Year: 2021, Volume and Issue: 13(8), P. 1463 - 1463

Published: July 27, 2021

Hepatitis B virus (HBV) remains a major medical problem affecting at least 257 million chronically infected patients who are risk of developing serious, frequently fatal liver diseases. HBV is small, partially double-stranded DNA that goes through an intricate replication cycle in its native cellular environment: human hepatocytes. A critical step the viral life-cycle conversion relaxed circular (rcDNA) into covalently closed (cccDNA), latter being template for gene transcription. For this conversion, relies on multiple host factors, as enzymes capable catalyzing relevant reactions not encoded genome. Combinations genetic and biochemical approaches have produced findings provide more holistic picture complex mechanism cccDNA formation. Here, we review some these studies helped to comprehensive rcDNA conversion. Mechanistic insights persistence hold key devising new therapies will lead only suppression but cure.

Language: Английский

Citations

82
Epigenetic modulation in chronic hepatitis B virus infection DOI Creative Commons
Maura Dandri

Seminars in Immunopathology, Journal Year: 2020, Volume and Issue: 42(2), P. 173 - 185

Published: March 17, 2020

The human hepatitis B virus (HBV) is a small-enveloped DNA causing acute and chronic hepatitis. Despite the existence of an effective prophylactic vaccine strong capacity approved antiviral drugs to suppress viral replication, HBV infection (CHB) continues be major health burden worldwide. Both inability immune system resolve CHB unique replication strategy employed by HBV, which forms stable covalently closed circular (cccDNA) minichromosome in hepatocyte nucleus, enable persistence. Knowledge complex network interactions that engages with its host still limited but accumulating evidence indicates epigenetic modifications occurring both on cccDNA genome course are essential modulate activity likely contribute pathogenesis cancer development. Thus, deeper understanding regulatory processes may open new venues control eventually cure CHB. This review summarizes findings research, focusing mechanisms regulating determined infected cells tumor liver tissues.

Language: Английский

Citations

76
Therapeutic shutdown of HBV transcripts promotes reappearance of the SMC5/6 complex and silencing of the viral genome in vivo DOI Creative Commons
Lena Allweiss, Katja Giersch,

Andrea Pirosu

et al.

Gut, Journal Year: 2021, Volume and Issue: 71(2), P. 372 - 381

Published: Jan. 28, 2021

Objective Therapeutic strategies silencing and reducing the hepatitis B virus (HBV) reservoir, covalently closed circular DNA (cccDNA), have potential to cure chronic HBV infection. We aimed investigate impact of small interferring RNA (siRNA) targeting all transcripts or pegylated interferon-α (peg-IFNα) on viral regulatory HBx protein structural maintenance chromosome 5/6 complex (SMC5/6), a host factor suppressing cccDNA transcription. In particular, we assessed whether interventions lowering can achieve maintain transcription in vivo. Design HBV-infected human liver chimeric mice were treated with siRNA peg-IFNα. Virological changes analysed at end treatment during rebound phase by qualitative PCR, ELISA, immunoblotting chromatin immunoprecipitation. situ hybridisation was combined immunofluorescence detect SMC6 RNAs single cell level. The entry inhibitor myrcludex-B used avoid new infection events. Results Both peg-IFNα strongly reduced markers, including levels, thus enabling reappearance SMC5/6 hepatocytes that achieved HBV-RNA negativisation association cccDNA. Only IFN loads enhanced IFN-stimulated genes. However, antiviral effects did not persist off again degraded. Remarkably, blockade started hindered renewed degradation SMC5/6. Conclusion These results reveal therapeutics abrogating promote epigenetic suppression minichromosome, whereas protecting from reinfection are needed silencing.

Language: Английский

Citations

65
The Functions of Hepatitis B Virus Encoding Proteins: Viral Persistence and Liver Pathogenesis DOI Creative Commons

Fenglin Zhao,

Xiaoyu Xie, Xu Tan

et al.

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 12, 2021

About 250 million people worldwide are chronically infected with Hepatitis B virus (HBV), contributing to a large burden on public health. Despite the existence of vaccines and antiviral drugs prevent infection suppress viral replication respectively, chronic hepatitis (CHB) cure remains remote treatment goal. The persistence caused by HBV is account for which increases risk developing liver cirrhosis hepatocellular carcinoma (HCC). virion utilizes various strategies escape surveillance host immune system therefore enhancing its replication, while precise mechanisms involved remain elusive. Accumulating evidence suggests that proteins encoded (hepatitis surface antigen, core envelope HBx polymerase) play an important role in pathogenesis. This review summarizes major findings functions encoding proteins, illustrating how these affect hepatocytes system, may open new venues CHB therapies.

Language: Английский

Citations

58