-
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 -
Clinical and Molecular Hepatology Sep 2014Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its... (Review)
Review
Prediction of liver fibrosis progression has a key role in the management of chronic viral hepatitis, as it will be translated into the future risk of cirrhosis and its various complications including hepatocellular carcinoma. Both hepatitis B and C viruses mainly lead to fibrogenesis induced by chronic inflammation and a continuous wound healing response. At the same time direct and indirect profibrogenic responses are also elicited by the viral infection. There are a handful of well-established risk factors for fibrosis progression including older age, male gender, alcohol use, high viral load and co-infection with other viruses. Metabolic syndrome is an evolving risk factor of fibrosis progression. The new notion of regression of advanced fibrosis or even cirrhosis is now strongly supported various clinical studies. Even liver biopsy retains its important role in the assessment of fibrosis progression, various non-invasive assessments have been adopted widely because of their non-invasiveness, which facilitates serial applications in large cohorts of subjects. Transient elastography is one of the most validated tools which has both diagnostic and prognostic role. As there is no single perfect test for liver fibrosis assessment, algorithms combining the most validated noninvasive methods should be considered as initial screening tools.
Topics: Age Factors; Antiviral Agents; Biomarkers; Hepatitis, Chronic; Hepatitis, Viral, Human; Humans; Liver; Liver Cirrhosis; Orthohepadnavirus; Risk Factors; Ultrasonography
PubMed: 25320725
DOI: 10.3350/cmh.2014.20.3.228 -
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 -
Journal of Hepatology May 2017
Topics: Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunity, Innate; Liver
PubMed: 28223100
DOI: 10.1016/j.jhep.2017.02.006 -
Alimentary Pharmacology & Therapeutics Jan 2022
Topics: Adenine; Hepatitis B virus; Humans; Tenofovir
PubMed: 34907570
DOI: 10.1111/apt.16668 -
Alimentary Pharmacology & Therapeutics Jan 2022
Topics: Adenine; Hepatitis B virus; Humans; Tenofovir
PubMed: 34907550
DOI: 10.1111/apt.16692 -
Viruses Apr 2017Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was... (Review)
Review
Hepatitis B X protein (HBx) plays an essential role in the hepatitis B virus (HBV) replication cycle, but the function of HBx has been elusive until recently. It was recently shown that transcription from the HBV genome (covalently-closed circular DNA, cccDNA) is inhibited by the structural maintenance of chromosome 5/6 complex (Smc5/6), and that a key function of HBx is to redirect the DNA-damage binding protein 1 (DDB1) E3 ubiquitin ligase to target this complex for degradation. By doing so, HBx alleviates transcriptional repression by Smc5/6 and stimulates HBV gene expression. In this review, we discuss in detail how the interplay between HBx and Smc5/6 was identified and characterized. We also discuss what is known regarding the repression of cccDNA transcription by Smc5/6, the timing of HBx expression, and the potential role of HBx in promoting hepatocellular carcinoma (HCC).
Topics: Cell Cycle Proteins; Chromosomal Proteins, Non-Histone; Hepatitis B virus; Host-Pathogen Interactions; Humans; Trans-Activators; Viral Regulatory and Accessory Proteins; Virus Replication
PubMed: 28368357
DOI: 10.3390/v9040069 -
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