ArticleHepatology (Baltimore, Md.)2020
Hepatitis B Virus Virions Produced Under Nucleos(t)ide Analogue Treatment Are Mainly Not Infectious Because of Irreversible DNA Chain Termination.
Article in Hepatology (Baltimore, Md.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- Mitochondrial-Based Nanomedicine in Treatment of Liver Cancer.Molecular biotechnology · 2026Review
- Functional cure for chronic hepatitis B: A state of immune control over cccDNA persistence.Infectious diseases & immunity · 2026Review
- [Comparison of antiviral efficacy of nucleos(t)ide analogue monotherapy and its combination with interferon-α in children 1-6 years-old with HBeAg-positive chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- Performance Evaluation of a HBsAg-Specific Immunoadsorbent Based on a Humanized Anti-HBsAg Monoclonal Antibody.Biomedicines · 2025Article
- HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.PLoS pathogens · 2025Article
- Longitudinal profile of plasma pregenomic RNA in patients with chronic hepatitis B infection on long-term nucleoside analogues and its interaction with clinical parameters.Clinical and molecular hepatology · 2025Article
- Development of a dual channel detection system for pan-genotypic simultaneous quantification of hepatitis B and delta viruses.Emerging microbes & infections · 2024Article
- Latest insights into the epidemiology, characteristics, and therapeutic strategies of chronic hepatitis B patients in indeterminate phase.European journal of medical research · 2024Review
- Liver-specific Mettl14 deletion induces nuclear heterotypia and dysregulates RNA export machinery.bioRxiv : the preprint server for biology · 2024Article
- [Research progress on the effect of hepatitis B virus DNA integration on antiviral therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Review
- Targeted viral adaptation generates a simian-tropic hepatitis B virus that infects marmoset cells.Nature communications · 2023Article
- Article
- Sera of Individuals Chronically Infected with Hepatitis B Virus (HBV) Contain Diverse RNA Types Produced by HBV Replication or Derived from Integrated HBV DNA.Journal of virology · 2023Article
- Diversity of the nucleic acid forms of circulating HBV in chronically infected patients and its impact on viral cycle.Hepatology international · 2022Article
- A standardized assay for the quantitative detection of serum HBV RNA in chronic hepatitis B patients.Emerging microbes & infections · 2022Article
- Molecular clones of genetically distinct hepatitis B virus genotypes reveal distinct host and drug treatment responses.JHEP reports : innovation in hepatology · 2022Article
- Effectiveness of antiviral treatment in HBeAg-negative chronic hepatitis B patients with normal or mildly elevated alanine aminotransferase: a retrospective study.BMC gastroenterology · 2022Article
- [Expert consensus on measurement and clinical application of serum HBV RNA in patients with chronic HBV infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- [A short half-life of cccDNA offer or ignite hope for hepatitis B cure under nucleos(t)ide analogues treatment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
- [A possible mechanism for low-level viremia occurrence in nucleos(t)ide analog-treated chronic hepatitis B patients].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2021Article
Corrections and comments
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Authors and funding
20 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleos(t)ide analogues (NAs) have been widely used for the treatment of chronic hepatitis B (CHB). Because viral DNA polymerase lacks proofreading function (3' exonuclease activity), theoretically, the incorporated NAs would irreversibly terminate viral DNA synthesis. This study explored the natures of nascent hepatitis B virus (HBV) DNA and infectivity of progeny virions produced under NA treatment. HBV infectivity was determined by infection of HepG2-NTCP cells and primary human hepatocytes (PHHs). Biochemical properties of HBV DNA in the progeny virions were investigated by qPCR, northern blotting, or Southern blotting hybridization, sucrose gradient centrifugation, and in vitro endogenous DNA polymerase assay. Progeny HBV virions produced under NA treatment were mainly not infectious to HepG2-NTCP cells or PHHs. Biochemical analysis revealed that under NA treatment, HBV DNA in nucleaocapsids or virions were predominantly short minus-strand DNA with irreversible termination. This finding was supported by the observation of first disappearance of relaxed circular DNA and then the proportional decline of HBV-DNA levels corresponding to the regions of PreC/C, S, and X genes in serial sera of patients receiving NA treatment. Conclusion: HBV virions produced under NA treatment are predominantly replication deficient because the viral genomes are truncated and elongation of DNA chains is irreversibly terminated. Clinically, our results suggest that the viral loads of CHB patients under NA therapy vary with the different regions of genome being detected by qPCR assays. Our findings also imply that NA prevention of perinatal and sexual HBV transmission as well as infection of transplanted livers works not only by reducing viral loads, but also by producing noninfectious virions.
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