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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 Apr 2018This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated....
This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription. Its covalently closed circular (ccc) DNA in the nucleus encodes a pregenomic RNA (pgRNA), which can be encapsidated by HBV polymerase. Reverse transcription occurs in the capsids by using the pgRNA as a template for the synthesis of single-stranded linear and then partially double-stranded relaxed circular (rc) DNA. Capsids containing a mature rc DNA genome target to the nucleus for ccc DNA synthesis. Persistent HBV infection is caused mainly by ccc DNA and immune tolerance to HBV antigens in the liver. Unlike acute infection, chronic carriers contain only a low level of HBV core-antigen-specific T cell activity, contributing to the lack of viral clearance.
Topics: Animals; Antigens, Viral; Disease Models, Animal; Hepatitis B; Hepatitis B Vaccines; Hepatitis B virus; Humans; Nucleocapsid; Vaccines, Synthetic; Virion
PubMed: 29500037
DOI: 10.1016/j.tim.2018.01.009 -
Advances in Experimental Medicine and... 2020Chronic hepatitis B virus (HBV) infection remains to be a serious threat to public health and is associated with many liver diseases including chronic hepatitis B (CHB),... (Review)
Review
Chronic hepatitis B virus (HBV) infection remains to be a serious threat to public health and is associated with many liver diseases including chronic hepatitis B (CHB), liver cirrhosis, and hepatocellular carcinoma. Although nucleos(t)ide analogues (NA) and pegylated interferon-α (Peg-IFNα) have been confirmed to be efficient in inhibiting HBV replication, it is difficult to eradicate HBV and achieve the clinical cure of CHB. Therefore, long-term therapy has been recommended to CHB treatment under the current antiviral therapy. In this context, the new antiviral therapy targeting one or multiple critical steps of viral life cycle may be an alternative approach in future. In the last decade, the functional receptor [sodium-taurocholate cotransporting polypeptide (NTCP)] of HBV entry into hepatocytes has been discovered, and the immature nucleocapsids containing the non- or partially reverse-transcribed pregenomic RNA, the nucleocapsids containing double-strand linear DNA (dslDNA), and the empty particles devoid of any HBV nucleic acid have been found to be released into circulation, which have supplemented the life cycle of HBV. The understanding of HBV life cycle may offer a new instruction for searching the potential antiviral targets, and the new viral markers used to monitor the efficacy of antiviral therapy for CHB patients in the future.
Topics: Antiviral Agents; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Humans; Interferon-alpha; Virus Internalization; Virus Replication
PubMed: 31741332
DOI: 10.1007/978-981-13-9151-4_2 -
Nature Reviews. Disease Primers Jun 2018
Review
Topics: Hepatitis B; Hepatitis B virus; Humans; Quality of Life
PubMed: 29877317
DOI: 10.1038/nrdp.2018.36 -
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 -
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 -
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 -
Hepatology (Baltimore, Md.) Apr 2022
Topics: Demography; Hepatitis B virus; Mass Screening; United States
PubMed: 34951716
DOI: 10.1002/hep.32303 -
Hepatology (Baltimore, Md.) Jul 2021
Topics: DNA; Hepatitis B virus; RNA
PubMed: 33368408
DOI: 10.1002/hep.31689 -
Clinical Gastroenterology and... Feb 2020
Topics: Hepatitis B virus; Humans; Patient Dropouts
PubMed: 31352094
DOI: 10.1016/j.cgh.2019.07.040