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NDP52 mediates an antiviral response to hepatitis B virus infection through Rab9-dependent lysosomal degradation pathway
The nuclear dot protein 52 (NDP52) is an autophagy receptor known to trigger autophagy following bacterial infection. Here, Cui et al. show that NDP52 also triggers an anti-viral response following hepatitis B virus (HBV) infection. NDP52 forms a tripartite complex with Rab9 and envelope proteins of HBV and targets the virus to Rab9-dependent lysosomal degradation pathway.
- Shuzhi Cui
- , Tian Xia
- & Yu Wei
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Article
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Interferon stimulated immune profile changes in a humanized mouse model of HBV infection
There is increasing evidence that treatment of hepatitis B with interferon alpha can be beneficial. Here, Wang et al, present a type 1 interferon receptor humanized mouse model and characterize it as a platform in which to study interferon function in vivo.
- Yaping Wang
- , Liliangzi Guo
- & Feng Li
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Molecular insights into Spindlin1-HBx interplay and its impact on HBV transcription from cccDNA minichromosome
The mechanism by which the chromatinized HBV genome is transcribed remains poorly understood. In this study, Liu et al. demonstrate how HBx exploits Spindlin1, a histone methylation reader, to overcome heterochromatin barriers and enhance HBV transcription from the cccDNA minichromosome.
- Wei Liu
- , Qiyan Yao
- & Haitao Li
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Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells
Hepatitis B virus is an almost uniquely human-tropic pathogen for which model systems are scarce. Here, the authors determine key residues within the HBV receptor that form a barrier in the HBV life cycle in primates and identify marmosets as a model candidate for infection with simian-tropic HBV.
- Yongzhen Liu
- , Thomas R. Cafiero
- & Alexander Ploss
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Molecular elucidation of drug-induced abnormal assemblies of the hepatitis B virus capsid protein by solid-state NMR
Hepatitis B virus (HBV) capsid assembly modulators (CAM) represent a recent class of anti-HBV antivirals. Structural approaches provide limited conformational information on the CAM-induced off-path assemblies. Here, authors use solid-state NMR to establish a structural view on assembly modulation of the HBV capsid.
- Lauriane Lecoq
- , Louis Brigandat
- & Anja Böckmann
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Neutralization of hepatitis B virus with vaccine-escape mutations by hepatitis B vaccine with large-HBs antigen
The hepatitis B vaccine is recognised as the most effective approach in reducing hepatitis-B-related morbidity; vaccine-escape mutations are however capable of infecting vaccinated individuals. In this work, authors aim to establish a hepatitis B vaccine candidate, which they assess in rhesus macaques in terms of efficacy and safety.
- Ayaka Washizaki
- , Asako Murayama
- & Takanobu Kato
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A 33-residue peptide tag increases solubility and stability of Escherichia coli produced single-chain antibody fragments
Low solubility and stability of Escherichia coli produced single chain variable fragments (scFvs) restrict their applications. Here the authors report a 33-residue peptide tag which simultaneously increases the solubility and thermostability of multiple scFvs produced in Escherichia coli SHuffle strain.
- Yang Wang
- , Wenjie Yuan
- & Yong-Xiang Wang
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Long-term hepatitis B virus infection of rhesus macaques requires suppression of host immunity
Here, Biswas et al. present and characterize a second-generation model of HBV infection in rhesus macaques, showing that extended infection requires suppression of host immunity.
- Sreya Biswas
- , Lauren N. Rust
- & Benjamin J. Burwitz
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Targeting human Acyl-CoA:cholesterol acyltransferase as a dual viral and T cell metabolic checkpoint
Shared metabolic pathways could allow simultaneous manipulation of T cells, viruses and tumours. Here the authors show targeting cholesterol esterification restrains hepatitis B in vitro, whilst bolstering exhausted antigen-specific T cell responses from human liver and hepatocellular carcinoma.
- Nathalie M. Schmidt
- , Peter A. C. Wing
- & Mala K. Maini
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Circadian control of hepatitis B virus replication
The circadian factors BMAL1/CLOCK and REV-ERB are master regulators of the human liver transcriptome but their role in hepatitis B virus infection is largely unknown. Here, Zhuang et al. show that REV-ERB regulates hepatitis B virus entry and BMAL1 directly binds HBV DNA and activates viral genome transcription.
- Xiaodong Zhuang
- , Donall Forde
- & Jane A. McKeating
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Hepatitis B virus cccDNA is formed through distinct repair processes of each strand
HBV covalently closed circular DNA (cccDNA) enables and persists in chronic infection, but the molecular mechanism of its formation is unclear. Here, Wei and Ploss elucidate the detailed kinetics and biochemical steps by which the relaxed circular DNA is converted into cccDNA.
- Lei Wei
- & Alexander Ploss
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Hepatitis B virus rigs the cellular metabolome to avoid innate immune recognition
RIG-I is a cytosolic antiviral nucleic acid sensor that signals via MAVS to produce type 1 interferons. Here the authors show that hepatits B virus can repress this pathway by activating glycolysis and lactate production, enabling accumulated lactate to bind MAVS and prevent its mitochondrial localization.
- Li Zhou
- , Rui He
- & Shi Liu
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A genome-wide gain-of-function screen identifies CDKN2C as a HBV host factor
Here the authors perform a gain-of-function screen and identify CDKN2C as a host factor for HBV replication, inducing cell cycle arrest and expression of HBV transcription enhancers. CDKN2C expression correlates with disease progression suggesting a potential role in HBV-induced liver disease.
- Carla Eller
- , Laura Heydmann
- & Thomas F. Baumert
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Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction
Hepatitis B virus X protein (HBx) binds anti-apoptotic Bcl-xL through its BH3-like motif to promote viral replication. Here, the authors provide the structure of the HBx BH3-like domain and Bcl-xL, which shows an unusual mode of interaction, and identify a short peptide that inhibits HBV replication in cultured human hepatic cells.
- Tian-Ying Zhang
- , Hong-Ying Chen
- & Y. Adam Yuan
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Ciclopirox inhibits Hepatitis B Virus secretion by blocking capsid assembly
Current treatments for chronic hepatitis B virus (HBV) infection are not curative. Here, the authors show that an antifungal drug, ciclopirox, inhibits HBV capsid assembly and synergizes with nucleoside/nucleotide analogs to prevent HBV replication in cells and in a humanized liver mouse model.
- Jung-Ah Kang
- , Songwon Kim
- & Sung-Gyoo Park
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Enveloped viruses distinct from HBV induce dissemination of hepatitis D virus in vivo
Hepatitis D virus (HDV) relies on a helper virus to package and transmit its ribonucleoprotein (RNP). Here, Perez-Vargas et al. show that HDV can use envelope proteins from HBV-unrelated viruses, including HCV and flaviviruses, to propagate in vitro and in humanized mice.
- Jimena Perez-Vargas
- , Fouzia Amirache
- & François-Loïc Cosset
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Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin
Whether DNA viruses contact specific regions of host genomes or make random contacts is unclear. Here, the authors use Hi-C and show that HBV cccDNA and Ad5 DNA contact preferentially active chromatin at CpG islands for the former and at transcription start sites and enhancers for the latter.
- Pierrick Moreau
- , Axel Cournac
- & Christine Neuveut
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Intracellular interleukin-32γ mediates antiviral activity of cytokines against hepatitis B virus
Cytokines such as TNF and IFN-γ are important for immunity against hepatitis B virus (HBV). Here the authors show that interleukin-32 gamma (IL-32γ) acts downstream of TNF and IFN-γ as an intracellular effector, and that IL-32γ negatively regulates host factors contributing to HBV transcription to promote HBV clearance.
- Doo Hyun Kim
- , Eun-Sook Park
- & Kyun-Hwan Kim
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3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection
Long-term in vitro models for hepatitis B virus (HBV) infection are important to understand this infection, but are lacking. Here the authors develop a microfluidic primary human hepatocyte organoid culture system that can be maintained over 40 days and recapitulates all of the steps of the HBV life cycle.
- A. M. Ortega-Prieto
- , J. K. Skelton
- & M. Dorner
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Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques
Hepatitis B virus (HBV) has a limited host range and current animal models can only recapitulate certain aspects of HBV replication. Here, the authors show that expression of the HBV receptor NTCP in macaques supports HBV replication in vivo, suggesting this as animal model for future HBV studies.
- Benjamin J. Burwitz
- , Jochen M. Wettengel
- & Jonah B. Sacha
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Hepatitis B virus persistence in mice reveals IL-21 and IL-33 as regulators of viral clearance
Hepatitis B virus (HBV) establishes chronic infection in only some patients, but the mechanisms underlying clearance failure in these patients are not fully understood. Here, the authors identify and characterize an HBV strain that can persist in mice and show that IL-21 and IL-33 responses contribute to clearance.
- Zhongliang Shen
- , Huijuan Yang
- & Jing Liu
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Long-term hepatitis B infection in a scalable hepatic co-culture system
The lack of models that mimic hepatitis B virus (HBV) infection in a physiologically relevant context has hampered drug development. Here, Winer et al. establish a self-assembling, primary hepatocyte co-culture system that can be infected with patient-derived HBV without further modifications.
- Benjamin Y. Winer
- , Tiffany S. Huang
- & Alexander Ploss
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Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
This genome-wide association study on persistent hepatitis B virus (HBV) infection among Chinese confirms previously associated genetic loci while discovering a novel protective locus at 8p21.3. The study also demonstrates the nearby gene INST10 suppresses HBV replication in vitro.
- Yuanfeng Li
- , Lanlan Si
- & Gangqiao Zhou
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The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses
With paleovirology it is possible to identify ancient endogenous viral elements within eukaryotic genomes. Here Suh and colleagues report a genomic record of hepatitis endogenizations through bird’s evolution; they find a complete hepatitis genome sequence, the first discovery of a Mesozoic paleovirus genome.
- Alexander Suh
- , Jürgen Brosius
- & Jan Ole Kriegs
Origin and dispersal history of Hepatitis B virus in Eastern Eurasia