ArticleJournal of virology2016
In Vitro Studies Show that Sequence Variability Contributes to Marked Variation in Hepatitis B Virus Replication, Protein Expression, and Function Observed across Genotypes.
Article in Journal of virology, 2016. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- Hepatitis B surface antigen is upregulated by HIV Tat in an HIV-hepatitis B virus co-infection model system.Microbiology spectrum · 2025Article
- Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.Nature communications · 2024Article
- TheJournal of virology · 2024Article
- Hepatitis B Surface Antigen Isoforms: Their Clinical Implications, Utilisation in Diagnosis, Prevention and New Antiviral Strategies.Pathogens (Basel, Switzerland) · 2024Review
- Hepatitis B Virus Genotype Influence on Virological and Enzymatic Measures over Time-A Retrospective Longitudinal Cohort Study.Journal of clinical medicine · 2023Article
- Review
- An enrichment protocol and analysis pipeline for long read sequencing of the hepatitis B virus transcriptome.The Journal of general virology · 2023Article
- The role of hepatitis B virus genome variations in HBV-related HCC: effects on host signaling pathways.Frontiers in microbiology · 2023Review
- Molecular clones of genetically distinct hepatitis B virus genotypes reveal distinct host and drug treatment responses.JHEP reports : innovation in hepatology · 2022Article
- In vitro investigation of HBV clinical isolates from Chinese patients reveals that genotype C isolates possess higher infectivity than genotype B isolates.Virologica Sinica · 2022Article
- The Relationship Between Collagen Proportionate Area and Hepatitis B Surface Antigen Levels in E Antigen Positive Hepatitis B Cirrhosis.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Molecular and biological characterization of hepatitis B virus subgenotype F1b clusters: Unraveling its role in hepatocarcinogenesis.Frontiers in microbiology · 2022Article
- Infection courses, virological features and IFN-α responses of HBV genotypes in cell culture and animal models.Journal of hepatology · 2021Article
- Clinical stage drugs targeting inhibitor of apoptosis proteins purge episomal Hepatitis B viral genome in preclinical models.Cell death & disease · 2021Article
- A PCR assay to quantify patterns of HBV transcription.The Journal of general virology · 2021Article
- Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes.Microbial genomics · 2021Article
- Biological Characterization of Hepatitis B virus Genotypes: Their Role in Viral Replication and Antigen Expression.Frontiers in microbiology · 2021Article
- Key mutations in the C-terminus of the HBV surface glycoprotein correlate with lower HBsAg levelsEmerging microbes & infections · 2020Article
- The evolution and clinical impact of hepatitis B virus genome diversity.Nature reviews. Gastroenterology & hepatology · 2020Review
- Intrahepatic CXCL10 is strongly associated with liver fibrosis in HIV-Hepatitis B co-infection.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The hepatitis B virus (HBV) exists as 9 major genotypes (A to I), one minor strain (designated J) and multiple subtypes. Marked differences in HBV natural history, disease progression and treatment response are exhibited by many of these genotypes and subtypes. For example, HBV genotype C is associated with later hepatitis B e antigen (HBeAg) seroconversion and high rates of liver cancer compared to other HBV genotypes, whereas genotype A2 is rarely associated with HBeAg-negative disease or liver cancer. The reasons for these and other differences in HBV natural history are yet to be determined but could in part be due to sequence differences in the HBV genome that alter replicative capacity and/or gene expression. Direct comparative studies on HBV replication and protein expression have been limited to date due largely to the absence of infectious HBV cDNA clones for each of the HBV genotypes present in the same genetic arrangement. We have produced replication-competent infectious cDNA clones of the most common subtypes of genotypes A to D, namely, A2, B2, C2, D3, and the minor strain J, and compared their HBV replication phenotype using transient-transfection models. We identified striking differences in HBV replicative capacity as well as HBeAg and surface (HBsAg) protein expression across genotypes, which may in part be due to sequence variability in regulatory regions of the HBV genome. Functional analysis showed that sequence differences in the major upstream regulatory region across genotypes impacted promoter activity. IMPORTANCE: There have been very few studies directly comparing the replication phenotype of different HBV genotypes, for which there are marked differences in natural history and disease progression worldwide. We have generated replication-competent 1.3-mer cDNA clones of the major genotypes A2, B2, C2, and D3, as well as a recently identified strain J, and identified striking differences in replicative capacity and protein expression that may contribute to some of the observed differences in HBV natural history observed globally.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.