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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 -
Hepatology (Baltimore, Md.) May 2009Hepatitis 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...
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 -
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 -
The Journal of General Virology Jun 2020The 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,... (Review)
Review
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 -
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 -
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 -
Human Genetics Jun 2020In rare cases, hepatitis A virus (HAV) and hepatitis B virus (HBV) can cause fulminant viral hepatitis (FVH), characterized by massive hepatocyte necrosis and an... (Review)
Review
In rare cases, hepatitis A virus (HAV) and hepatitis B virus (HBV) can cause fulminant viral hepatitis (FVH), characterized by massive hepatocyte necrosis and an inflammatory infiltrate. Other viral etiologies of FVH are rarer. FVH is life-threatening, but the patients are typically otherwise healthy, and normally resistant to other microbes. Only a small minority of infected individuals develop FVH, and this is the key issue to be addressed for this disease. In mice, mouse hepatitis virus 3 (MHV3) infection is the main model for dissecting FVH pathogenesis. Susceptibility to MHV3 differs between genetic backgrounds, with high and low mortality in C57BL6 and A/J mice, respectively. FVH pathogenesis in mice is related to uncontrolled inflammation and fibrinogen deposition. In humans, FVH is typically sporadic, but rare familial forms also exist, suggesting that there may be causal monogenic inborn errors. A recent study reported a single-gene inborn error of human immunity underlying FVH. A patient with autosomal recessive complete IL-18BP deficiency was shown to have FVH following HAV infection. The mechanism probably involves enhanced IL-18- and IFN-γ-dependent killing of hepatocytes by NK and CD8 T cytotoxic cells. Proof-of-principle that FVH can be genetic is important clinically, for the affected patients and their families, and immunologically, for the study of immunity to viruses in the liver. Moreover, the FVH-causing IL18BP genotype suggests that excessive IL-18 immunity may be a general mechanism underlying FVH, perhaps through the enhancement of IFN-γ immunity.
Topics: Cytokines; Hepadnaviridae; Hepatitis, Viral, Human; Humans
PubMed: 32285199
DOI: 10.1007/s00439-020-02166-y -
Virology Journal May 2021Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently... (Review)
Review
BACKGROUND
Hepatitis B virus (HBV) is a DNA virus belonging to the Hepadnaviridae family that has limited tissue and species specificity. Due to the persistence of HBV covalently closed circular DNA (cccDNA) in host cells after HBV infection, current antiviral drugs cannot eradicate HBV. Therefore, the development of an active cell culture system supporting HBV infection has become the key to studying HBV and developing effective therapeutic drugs.
MAIN BODY
This review summarizes the significant research achievements in HBV cell culture systems in vitro, including embryonic hepatocytes and primary hepatocytes, which support the virus infection process most similar to that in the body and various liver tumor cells. The discovery of the bile-acid pump sodium-taurocholate co-transporting polypeptide (NTCP) as the receptor of HBV has advanced our understanding of HBV biology. Subsequently, various liver cancer cells overexpressing NTCP that support HBV infection have been established, opening a new door for studying HBV infection. The fact that induced pluripotent stem cells that differentiate into hepatocyte-like cells support HBV infection provides a novel idea for the establishment of an HBV cell culture system.
CONCLUSION
Because of the host and tissue specificity of HBV, a suitable in vitro HBV infection system is critical for the study of HBV pathogenesis. Nevertheless, recent advances regarding HBV infection in vitro offer hope for better studying the biological characteristics of HBV, the pathogenesis of hepatitis B, the screening of anti-HBV drugs and the mechanism of carcinogenesis.
Topics: Hep G2 Cells; Hepatitis B; Hepatitis B virus; Hepatocytes; Humans; Virus Replication
PubMed: 34051803
DOI: 10.1186/s12985-021-01580-6