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Antiviral Research Oct 2020Hepatitis B virus (HBV) specifically infects hepatocytes and causes severe liver diseases. The HBV life cycle is unique in that the genomic DNA (relaxed-circular... (Review)
Review
Hepatitis B virus (HBV) specifically infects hepatocytes and causes severe liver diseases. The HBV life cycle is unique in that the genomic DNA (relaxed-circular partially double-stranded DNA: rcDNA) is converted to a molecular template DNA (covalently closed circular DNA: cccDNA) to amplify a viral RNA intermediate, which is then reverse-transcribed back to viral DNA. The highly stable characteristics of cccDNA result in chronic infection and a poor rate of cure. This complex life cycle of HBV offers a variety of targets to develop antiviral agents. We provide here an update on the current knowledge of HBV biology and its life cycle, which may help to identify new antiviral targets.
Topics: Antiviral Agents; DNA, Viral; Hep G2 Cells; Hepatitis B; Hepatitis B virus; Hepatocytes; Host Microbial Interactions; Humans; Virus Replication
PubMed: 32866519
DOI: 10.1016/j.antiviral.2020.104925 -
Trends in Microbiology Jan 2018Hepatitis B virus (HBV) chronically infects 250 million people worldwide, resulting in nearly one million deaths annually. Studies in recent years have significantly... (Review)
Review
Hepatitis B virus (HBV) chronically infects 250 million people worldwide, resulting in nearly one million deaths annually. Studies in recent years have significantly improved our knowledge on the mechanisms of HBV persistence. HBV uses multiple pathways to harness host innate immunity to enhance its replication. It can also take advantage of the developing immune system and the not-yet-stabilized gut microbiota of young children to facilitate its persistence, and use maternal viral e antigen to educate immunity of the offspring to support its persistence after vertical transmission. The knowledge gained from these recent studies paves the way for the development of new therapies for the treatment of chronic HBV infection, which has so far been very challenging.
Topics: Age Factors; Child; Gastrointestinal Microbiome; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Host-Pathogen Interactions; Humans; Immunity, Innate; Infectious Disease Transmission, Vertical; Life Cycle Stages; Maternal Inheritance; Microbiota; Viral Load
PubMed: 28823759
DOI: 10.1016/j.tim.2017.07.006 -
Emerging Microbes & Infections Dec 2021Hepatitis B virus (HBV) is a DNA virus with a complex life cycle that includes a reverse transcription step. HBV is poorly sensed by the immune system and frequently... (Review)
Review
Hepatitis B virus (HBV) is a DNA virus with a complex life cycle that includes a reverse transcription step. HBV is poorly sensed by the immune system and frequently establishes persistent infection that can cause chronic infection, the leading cause of liver cancer and cirrhosis worldwide. Recent mounting evidence has indicated the growing importance of RNA methylation (m6A modification) in viral replication, immune escape, and carcinogenesis. The value of m6A RNA modification for the prediction and clinical management of chronic HBV infection remains to be assessed. However, a number of studies indicate the important role of m6A-marked transcripts and factors of m6A machinery in managing HBV-related pathologies. In this review, we discuss the fundamental and potential clinical impact of m6A modifications on HBV infection and pathogenesis, as well as highlight the important molecular techniques and tools that can be used for studying RNA m6A methylome.
Topics: Animals; Hepatitis B; Hepatitis B virus; Host-Pathogen Interactions; Humans; Liver Neoplasms; Methylation
PubMed: 34767497
DOI: 10.1080/22221751.2021.2006580 -
Viruses May 2023Virus-like particles (VLPs) have gained a lot of interest within the past two decades. The use of VLP-based vaccines to protect against three infectious agents-hepatitis... (Review)
Review
Virus-like particles (VLPs) have gained a lot of interest within the past two decades. The use of VLP-based vaccines to protect against three infectious agents-hepatitis B virus, human papillomavirus, and hepatitis E virus-has been approved; they are very efficacious and offer long-lasting immune responses. Besides these, VLPs from other viral infectious agents (that infect humans, animals, plants, and bacteria) are under development. These VLPs, especially those from human and animal viruses, serve as stand-alone vaccines to protect against viruses from which the VLPs were derived. Additionally, VLPs, including those derived from plant and bacterial viruses, serve as platforms upon which to display foreign peptide antigens from other infectious agents or metabolic diseases such as cancer, i.e., they can be used to develop chimeric VLPs. The goal of chimeric VLPs is to enhance the immunogenicity of foreign peptides displayed on VLPs and not necessarily the platforms. This review provides a summary of VLP vaccines for human and veterinary use that have been approved and those that are under development. Furthermore, this review summarizes chimeric VLP vaccines that have been developed and tested in pre-clinical studies. Finally, the review concludes with a snapshot of the advantages of VLP-based vaccines such as hybrid/mosaic VLPs over conventional vaccine approaches such as live-attenuated and inactivated vaccines.
Topics: Animals; Humans; Vaccines, Virus-Like Particle; Viruses; Hepatitis B virus; Vaccine Development
PubMed: 37243195
DOI: 10.3390/v15051109 -
Journal of Translational Medicine Jun 2023Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation...
BACKGROUND
Acute-on-chronic liver failure (ACLF) is a severe syndrome with high short-term mortality, but the pathophysiology still remains largely unknown. Immune dysregulation and metabolic disorders contribute to the progression of ACLF, but the crosstalk between immunity and metabolism during ACLF is less understood. This study aims to depict the immune microenvironment in the liver during ACLF, and explore the role of lipid metabolic disorder on immunity.
METHODS
Single-cell RNA-sequencing (scRNA-seq) was performed using the liver non-parenchymal cells (NPCs) and peripheral blood mononuclear cells (PBMCs) from healthy controls, cirrhosis patients and ACLF patients. A series of inflammation-related cytokines and chemokines were detected using liver and plasma samples. The lipid metabolomics targeted free fatty acids (FFAs) in the liver was also detected.
RESULTS
The scRNA-seq analysis of liver NPCs showed a significant increase of monocytes/macrophages (Mono/Mac) infiltration in ACLF livers, whereas the resident Kupffer cells (KCs) were exhausted. A characterized TREM2 Mono/Mac subpopulation was identified in ACLF, and showed immunosuppressive function. Combined with the scRNA-seq data from PBMCs, the pseudotime analysis revealed that the TREM2 Mono/Mac were differentiated from the peripheral monocytes and correlated with lipid metabolism-related genes including APOE, APOC1, FABP5 and TREM2. The targeted lipid metabolomics proved the accumulation of unsaturated FFAs associated with α-linolenic acid (α-LA) and α-LA metabolism and beta oxidation of very long chain fatty acids in the ACLF livers, indicating that unsaturated FFAs might promote the differentiation of TREM2 Mono/Mac during ACLF.
CONCLUSIONS
The reprogramming of macrophages was found in the liver during ACLF. The immunosuppressive TREM2 macrophages were enriched in the ACLF liver and contributed to the immunosuppressive hepatic microenvironment. The accumulation of unsaturated FFAs in the ACLF liver promoted the reprogramming of the macrophages. It might be a potential target to improve the immune deficiency of ACLF patients through regulating lipid metabolism.
Topics: Humans; Lipid Metabolism; Acute-On-Chronic Liver Failure; Hepatitis B virus; Leukocytes, Mononuclear; Macrophages; Fatty Acid-Binding Proteins
PubMed: 37380987
DOI: 10.1186/s12967-023-04294-1 -
Zeitschrift Fur Gastroenterologie Jul 2021
Topics: Gastroenterology; Hepatitis B; Hepatitis B virus; Humans; Metabolic Diseases
PubMed: 34255317
DOI: 10.1055/a-1498-2512 -
Alimentary Pharmacology & Therapeutics Oct 2019This article is linked to Jiang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15381 and https://doi.org/10.1111/apt.15452.
This article is linked to Jiang et al papers. To view these articles, visit https://doi.org/10.1111/apt.15381 and https://doi.org/10.1111/apt.15452.
Topics: Hepatitis B virus; Humans
PubMed: 31591767
DOI: 10.1111/apt.15428 -
Antimicrobial Agents and Chemotherapy Aug 1997We report the development and isolation of a cell line, termed HepAD38, that replicates human hepatitis B virus (HBV) under conditions that can be regulated with...
We report the development and isolation of a cell line, termed HepAD38, that replicates human hepatitis B virus (HBV) under conditions that can be regulated with tetracycline. In the presence of the antibiotic, this cell line is free of virus due to the repression of pregenomic (pg) RNA synthesis. Upon removal of tetracycline from the culture medium, the cells express viral pg RNA, accumulate subviral particles in the cytoplasm that contain DNA intermediates characteristic of viral replication, and secrete virus-like particles into the supernatant. Since the HepAD38 cell line can produce high levels of HBV DNA, it should be useful for analyses of the viral replication cycle that depend upon viral DNA synthesis in a synchronized fashion. In addition, this cell line has been formatted into a high-throughput, cell-based assay that permits the large-scale screening of diverse compound libraries for new classes of inhibitors of HBV replication.
Topics: Cell Line; DNA, Viral; Hepatitis B virus; Hepatoblastoma; Humans; Liver Neoplasms; Protein Synthesis Inhibitors; RNA, Viral; Tetracycline; Transfection; Tumor Cells, Cultured; Virus Replication
PubMed: 9257747
DOI: 10.1128/AAC.41.8.1715 -
Zeitschrift Fur Gastroenterologie Jul 2021
Topics: Gastroenterology; Hepatitis B; Hepatitis B virus; Humans; Metabolic Diseases
PubMed: 34255314
DOI: 10.1055/a-1498-2680 -
Zeitschrift Fur Gastroenterologie Jul 2021
Topics: Gastroenterology; Hepatitis B; Hepatitis B virus; Humans; Metabolic Diseases
PubMed: 34255313
DOI: 10.1055/a-1498-2706