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Virology Aug 2023For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the...
For patients with cirrhosis, early diagnosis is the key to delaying the development of liver fibrosis and improving prognosis. This study aimed to investigate the clinical significance of TL1A, which is a susceptibility gene for hepatic fibrosis, and DR3 in the development of cirrhosis and fibrosis. We analyzed the expression of TL1A, DR3, and other inflammatory cytokines associated with liver fibrosis in serum and PBMCs in 200 patients.TL1A methylation level was lower in patients with HBV-associated LC than in the other groups. In addition, the mRNA level and serum of TL1A and DR3 expression levels were found to increase in the LC. Hypomethylation of the TL1A promoter is present in HBV-associated LC, and TL1A and DR3 are highly expressed in HBV-associated cirrhosis. These results indicate that TL1A and DR3 may play an important role in the pathogenesis of LC and TL1A methylation levels may serve as a noninvasive biomarker for early diagnosis and progression of LC.
Topics: Humans; Hepatitis B virus; Tumor Necrosis Factor Ligand Superfamily Member 15; Fibrosis; Liver Cirrhosis; Tumor Necrosis Factor-alpha
PubMed: 37321146
DOI: 10.1016/j.virol.2023.04.009 -
Nature Reviews. Gastroenterology &... Sep 2022
Topics: Hepatitis B virus; Hepatitis D; Hepatitis Delta Virus; Humans
PubMed: 35883011
DOI: 10.1038/s41575-022-00664-0 -
Nature Reviews. Gastroenterology &... Dec 2022
Topics: Humans; Antiviral Agents; Hepatitis B virus; DNA, Viral; Virus Replication
PubMed: 36207612
DOI: 10.1038/s41575-022-00700-z -
Nature Materials Sep 2021Broad-spectrum antiviral platforms that can decrease or inhibit viral infection would alleviate many threats to global public health. Nonetheless, effective technologies...
Broad-spectrum antiviral platforms that can decrease or inhibit viral infection would alleviate many threats to global public health. Nonetheless, effective technologies of this kind are still not available. Here, we describe a programmable icosahedral canvas for the self-assembly of icosahedral shells that have viral trapping and antiviral properties. Programmable triangular building blocks constructed from DNA assemble with high yield into various shell objects with user-defined geometries and apertures. We have created shells with molecular masses ranging from 43 to 925 MDa (8 to 180 subunits) and with internal cavity diameters of up to 280 nm. The shell interior can be functionalized with virus-specific moieties in a modular fashion. We demonstrate this virus-trapping concept by engulfing hepatitis B virus core particles and adeno-associated viruses. We demonstrate the inhibition of hepatitis B virus core interactions with surfaces in vitro and the neutralization of infectious adeno-associated viruses exposed to human cells.
Topics: DNA; Hepatitis B virus; Microscopy, Electron, Transmission; Nanoparticles
PubMed: 34127822
DOI: 10.1038/s41563-021-01020-4 -
Viruses Apr 2021Chronic hepatitis B virus (HBV) infection affects more than 250 million people worldwide, which greatly increases the risk for terminal liver diseases, such as liver... (Review)
Review
Chronic hepatitis B virus (HBV) infection affects more than 250 million people worldwide, which greatly increases the risk for terminal liver diseases, such as liver cirrhosis and hepatocellular carcinoma (HCC). Even though current approved antiviral therapies, including pegylated type I interferon (IFN) and nucleos(t)ide analogs, can effectively suppress viremia, HBV infection is rarely cured. Since HBV exhibits a narrow species tropism and robustly infects only humans and higher primates, progress in HBV research and preclinical testing of antiviral drugs has been hampered by the scarcity of suitable animal models. Fortunately, a series of surrogate animal models have been developed for the study of HBV. An increased understanding of the barriers towards interspecies transmission has aided in the development of human chimeric mice and has greatly paved the way for HBV research in vivo, and for evaluating potential therapies of chronic hepatitis B. In this review, we summarize the currently available animal models for research of HBV and HBV-related hepadnaviruses, and we discuss challenges and future directions for improvement.
Topics: Animals; Disease Models, Animal; Disease Susceptibility; Genome, Viral; Hepatitis B; Hepatitis B virus; Host-Pathogen Interactions; Humans; Mice; Mice, Transgenic; Pan troglodytes; Viral Tropism
PubMed: 33924793
DOI: 10.3390/v13050777 -
Journal of Hepatology Aug 2022
Topics: Biomarkers; Hepatitis B virus
PubMed: 35398461
DOI: 10.1016/j.jhep.2022.03.028 -
Analytical Chemistry Aug 2020Charge detection mass spectrometry is a single particle technique where the masses of individual ions are determined from simultaneous measurements of each ion's / ratio...
Charge detection mass spectrometry is a single particle technique where the masses of individual ions are determined from simultaneous measurements of each ion's / ratio and charge. The ions pass through a conducting cylinder, and the charge induced on the cylinder is detected. The cylinder is usually placed inside an electrostatic linear ion trap so that the ions oscillate back and forth through the cylinder. The resulting time domain signal is analyzed by fast Fourier transformation; the oscillation frequency yields the /, and the charge is determined from the magnitudes. The mass resolving power depends on the uncertainties in both quantities. In previous work, the mass resolving power was modest, around 30-40. In this work we report around an order of magnitude improvement. The improvement was achieved by coupling high-accuracy charge measurements (obtained with dynamic calibration) with higher resolution / measurements. The performance was benchmarked by monitoring the assembly of the hepatitis B virus (HBV) capsid. The HBV capsid assembly reaction can result in a heterogeneous mixture of intermediates extending from the capsid protein dimer to the icosahedral = 4 capsid with 120 dimers. Intermediates of all possible sizes were resolved, as well as some overgrown species. Despite the improved mass resolving power, the measured peak widths are still dominated by instrumental resolution. Heterogeneity makes only a small contribution. Resonances were observed in some of the / spectra. They result from ions with different masses and charges having similar / values. Analogous resonances are expected whenever the sample is a heterogeneous mixture assembled from a common building block.
Topics: Capsid; Capsid Proteins; Hepatitis B virus; Mass Spectrometry
PubMed: 32806905
DOI: 10.1021/acs.analchem.0c02133 -
Alimentary Pharmacology & Therapeutics Jan 2022
Topics: Adenine; Hepatitis B virus; Humans; Tenofovir
PubMed: 34907550
DOI: 10.1111/apt.16692 -
Alimentary Pharmacology & Therapeutics Jan 2022
Topics: Adenine; Hepatitis B virus; Humans; Tenofovir
PubMed: 34907570
DOI: 10.1111/apt.16668 -
International Journal of Molecular... Sep 2019Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has... (Review)
Review
Hepatitis B virus (HBV) infection is a major health problem affecting about 300 million people globally. Although successful administration of a prophylactic vaccine has reduced new infections, a cure for chronic hepatitis B (CHB) is still unavailable. Current anti-HBV therapies slow down disease progression but are not curative as they cannot eliminate or permanently silence HBV covalently closed circular DNA (cccDNA). The cccDNA minichromosome persists in the nuclei of infected hepatocytes where it forms the template for all viral transcription. Interactions between host factors and cccDNA are crucial for its formation, stability, and transcriptional activity. Here, we summarize the reported interactions between HBV cccDNA and various host factors and their implications on HBV replication. While the virus hijacks certain cellular processes to complete its life cycle, there are also host factors that restrict HBV infection. Therefore, we review both positive and negative regulation of HBV cccDNA by host factors and the use of small molecule drugs or sequence-specific nucleases to target these interactions or cccDNA directly. We also discuss several reporter-based surrogate systems that mimic cccDNA biology which can be used for drug library screening of cccDNA-targeting compounds as well as identification of cccDNA-related targets.
Topics: Animals; DNA, Circular; DNA, Viral; Hepatitis B; Hepatitis B virus; Hepatocytes; Humans; Virus Replication
PubMed: 31480501
DOI: 10.3390/ijms20174276