Review

Authors: Senko Tsukuda, Koichi Watashi

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

Authors: T Jake Liang

Hepatitis B virus (HBV) infects more than 300 million people worldwide and is a common cause of liver disease and liver cancer. HBV, a member of the Hepadnaviridae family, is a small DNA virus with unusual features similar to retroviruses. HBV replicates through an RNA intermediate and can integrate into the host genome. The unique features of the HBV replication cycle confer a distinct ability of the virus to persist in infected cells. Virological and serological assays have been developed for diagnosis of various forms of HBV-associated disease and for treatment of chronic hepatitis B infection. HBV infection leads to a wide spectrum of liver disease ranging from acute (including fulminant hepatic failure) to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Acute HBV infection can be either asymptomatic or present with symptomatic acute hepatitis. Most adults infected with the virus recover, but 5%-10% are unable to clear the virus and become chronically infected. Many chronically infected persons have mild liver disease with little or no long-term morbidity or mortality. Other individuals with chronic HBV infection develop active disease, which can progress to cirrhosis and liver cancer. These patients require careful monitoring and warrant therapeutic intervention. Extrahepatic manifestations of HBV infection are rare but can be difficult to diagnose and manage. The challenges in the area of HBV-associated disease are the lack of knowledge in predicting outcome and progression of HBV infection and an unmet need to understand the molecular, cellular, immunological, and genetic basis of various disease manifestations associated with HBV infection.

Topics: Hepatitis B virus; Hepatitis B, Chronic; Humans

PubMed: 19399811
DOI: 10.1002/hep.22881

Review

Authors: Diana Asema Asandem, Selorm Philip Segbefia, Kwadwo Asamoah Kusi...

Hepatitis B and C viruses (HBV and HCV) are the leading causes of end-stage liver disease worldwide. Although there is a potent vaccine against HBV, many new infections are recorded annually, especially in poorly resourced places which have lax vaccination policies. Again, as HBV has no cure and chronic infection is lifelong, vaccines cannot help those already infected. Studies to thoroughly understand the HBV biology and pathogenesis are limited, leaving much yet to be understood about the genomic features and their role in establishing and maintaining infection. The current knowledge of the impact on disease progression and response to treatment, especially in hyperendemic regions, is inadequate. This calls for in-depth studies on viral biology, mainly for the purposes of coming up with better management strategies for infected people and more effective preventative measures for others. This information could also point us in the direction of a cure. Here, we discuss the progress made in understanding the genomic basis of viral activities leading to the complex interplay of the virus and the host, which determines the outcome of HBV infection as well as the impact of coinfections.

Topics: Humans; Hepatitis B virus; Hepatitis B; Coinfection; Genome, Viral; Animals

PubMed: 38793606
DOI: 10.3390/v16050724

Review

Authors: Kuen-Nan Tsai, Cheng-Fu Kuo, Jing-Hsiung James Ou...

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

Review

Authors: Lars Magnius, William S Mason, John Taylor...

The family comprises small enveloped viruses with a partially double-stranded DNA genome of 3.0-3.4 kb. All family members express three sets of proteins (preC/C, polymerase and preS/S) and replication involves reverse transcription within nucleocapsids in the cytoplasm of hepatocytes. Hepadnaviruses are hepatotropic and infections may be transient or persistent. There are five genera: , , and . This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family which is available at ictv.global/report/hepadnaviridae.

Topics: Cytoplasm; Genome, Viral; Hepadnaviridae; Hepatocytes; Humans; Virus Replication

PubMed: 32416744
DOI: 10.1099/jgv.0.001415

Authors: Anna Pasetto, Gustaf Ahlén, Matti Sällberg...

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

Review

Authors: Andoni Gómez-Moreno, Alexander Ploss

Hepatitis B virus (HBV) is the etiologic agent of chronic hepatitis B, which puts at least 300 million patients at risk of developing fibrosis, cirrhosis, and hepatocellular carcinoma. HBV is a partially double-stranded DNA virus of the family. While HBV was discovered more than 50 years ago, many aspects of its replicative cycle remain incompletely understood. Central to HBV persistence is the formation of covalently closed circular DNA (cccDNA) from the incoming relaxed circular DNA (rcDNA) genome. cccDNA persists as a chromatinized minichromosome and is the major template for HBV gene transcription. Here, we review how cccDNA and the viral minichromosome are formed and how viral gene transcription is regulated and highlight open questions in this area of research.

Topics: Hepatitis B virus; DNA, Circular; Humans; DNA, Viral; Virus Replication; Viral Transcription; Gene Expression Regulation, Viral; Transcription, Genetic; Genome, Viral; Hepatitis B, Chronic; Hepatitis B; DNA Replication

PubMed: 38675950
DOI: 10.3390/v16040609

Review

Authors: Prakriti Sinha, Chloe L Thio, Ashwin Balagopal...

The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.

Topics: Hepatitis B virus; Virus Replication; Humans; Host-Pathogen Interactions; Hepatitis B; Hepatocytes; Animals

PubMed: 38793645
DOI: 10.3390/v16050764

Review

Authors: Babak Negahdari, Mohammad Darvishi, Ali Asghar Saeedi...

Hepatitis B virus (HBV) infection is one of the major health issues in the world presently with high tendency of leading to hepatocarcinoma, cirrhosis, and liver cancer, especially if not properly managed. It has been estimated that there are about 2 billion people with a serological profile of HBV infection, and 360 million patients worldwide living with chronic HBV-associated liver disease, hence the need to find an efficient and precise diagnosis technique to drive a robust treatment for Hepatitis B virus cannot be over emphasized. The emergence of analytical device like biosensor which combines biological and physicochemical element to detect HBV in screened samples has been very helpful in providing a timely intervention to tame this virus. This review focuses on the current state of biosensor researches with respect to various in-depth application of gold nanoparticle for the detection of hepatitis B virus (HBV).

Topics: Biosensing Techniques; Gold; Hepatitis B Surface Antigens; Hepatitis B virus; Metal Nanoparticles; Nanotechnology

PubMed: 30836779
DOI: 10.1080/21691401.2018.1553786

Authors: Alexander Suh, Claudia C Weber, Christian Kehlmaier...

Hepadnaviridae are double-stranded DNA viruses that infect some species of birds and mammals. This includes humans, where hepatitis B viruses (HBVs) are prevalent pathogens in considerable parts of the global population. Recently, endogenized sequences of HBVs (eHBVs) have been discovered in bird genomes where they constitute direct evidence for the coexistence of these viruses and their hosts from the late Mesozoic until present. Nevertheless, virtually nothing is known about the ancient host range of this virus family in other animals. Here we report the first eHBVs from crocodilian, snake, and turtle genomes, including a turtle eHBV that endogenized >207 million years ago. This genomic "fossil" is >125 million years older than the oldest avian eHBV and provides the first direct evidence that Hepadnaviridae already existed during the Early Mesozoic. This implies that the Mesozoic fossil record of HBV infection spans three of the five major groups of land vertebrates, namely birds, crocodilians, and turtles. We show that the deep phylogenetic relationships of HBVs are largely congruent with the deep phylogeny of their amniote hosts, which suggests an ancient amniote-HBV coexistence and codivergence, at least since the Early Mesozoic. Notably, the organization of overlapping genes as well as the structure of elements involved in viral replication has remained highly conserved among HBVs along that time span, except for the presence of the X gene. We provide multiple lines of evidence that the tumor-promoting X protein of mammalian HBVs lacks a homolog in all other hepadnaviruses and propose a novel scenario for the emergence of X via segmental duplication and overprinting of pre-existing reading frames in the ancestor of mammalian HBVs. Our study reveals an unforeseen host range of prehistoric HBVs and provides novel insights into the genome evolution of hepadnaviruses throughout their long-lasting association with amniote hosts.

Topics: Alligators and Crocodiles; Amino Acid Sequence; Animals; Base Sequence; Birds; Evolution, Molecular; Fossils; Genome; Genomics; Hepadnaviridae; Hepatitis B virus; Mammals; Molecular Sequence Data; Nucleic Acid Conformation; Phylogeny; Snakes; Turtles

PubMed: 25501991
DOI: 10.1371/journal.pgen.1004559