ArticleJournal of hepatology2017
Alternative splicing of hepatitis B virus: A novel virus/host interaction altering liver immunity.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Mapping the Heterogeneity of Histone Modifications on Hepatitis B Virus DNA Using Liver Needle Biopsies Obtained from Chronically Infected Patients.Journal of virology · 2019Trial
- TRMT6-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ddOTs: A multiplexed quantitative ddPCR approach for resolving overlapping hepatitis B virus transcripts to decipher cccDNA-driven transcription.PLoS pathogens · 2026Article
- Review
- Identification of Cyclin L1 as a Host Factor Regulating Hepatitis B Virus Replication.Viruses · 2026Article
- Molecular arms races at the virus-host splicing interface and their pathogenic implications.Frontiers in microbiology · 2026Review
- Decoding the interconnected splicing patterns of hepatitis B virus and host using large language and deep learning models.Microbial genomics · 2026Article
- Article
- Aberrant alternative splicing in alcoholic hepatitis: regulatory roles of RBPs and sQTLs.BMC gastroenterology · 2025Article
- Transcriptional responses of mouse proximal colon and colonoids during early whipworm infection.mBio · 2025Article
- High-dimensional droplet digital PCR of multiple hepatitis B splice variants in serum, liver, and tissue culture.Journal of virological methods · 2025Article
- HBV Remodels PP2A Complexes to Rewire Kinase Signaling in Hepatocellular Carcinoma.Cancer research · 2025Article
- Macrophage heterogeneity in liver fibrosis.Frontiers in immunology · 2025Review
- Genome-wide analysis of alternative splicing differences in hepatic ischemia reperfusion injury.Scientific reports · 2024Article
- Mechanisms underlying the compromised clinical efficacy of interferon in clearing HBV.Virology journal · 2024Review
- Alternative splicing and related RNA binding proteins in human health and disease.Signal transduction and targeted therapy · 2024Review
- The role and therapeutic targeting of the CCL2/CCR2 signaling axis in inflammatory and fibrotic diseases.Frontiers in immunology · 2024Review
- Genome-wide characterization of alternative splicing in blood cells of COVID-19 and respiratory infections of relevance.Virologica Sinica · 2023Article
- Protein Acetylation Increased Risk of Fibrosis-Related Liver Cancer.Journal of oncology · 2023Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsHepatitis B virus (HBV) RNA can undergo alternative splicing, but the relevance of this post-transcriptional regulation remains elusive. The mechanism of HBV alternative splicing regulation and its impact on liver pathogenesis were investigated.
methodsHBV RNA-interacting proteins were identified by RNA pull-down, combined with mass spectrometry analysis. HBV splicing regulation was investigated in chemically and surgically induced liver damage, in whole HBV genome transgenic mice and in hepatoma cells. Viral and endogenous gene expression were quantified by quantitative reverse transcription polymerase chain reaction, Western blot and enzyme-linked immunosorbent assay. Resident liver immune cells were studied by fluorescence-activated cell sorting.
resultsHBV pregenomic RNA-interacting proteins were identified and 15% were directly related to the splicing machinery. Expression of these splicing factors was modulated in HBV transgenic mice with liver injuries and contributed to an increase of the HBV spliced RNA encoding for HBV splicing-generated protein (HBSP). HBSP transgenic mice with chemically induced liver fibrosis exhibited attenuated hepatic damage. The protective effect of HBSP resulted from a decrease of inflammatory monocyte/macrophage recruitment through downregulation of C-C motif chemokine ligand 2 (CCL2) expression in hepatocytes. In human hepatoma cells, the ability of HBSP to control CCL2 expression was confirmed and maintained in a whole HBV context. Finally, viral spliced RNA detection related to a decrease of CCL2 expression in the livers of HBV chronic carriers underscored this mechanism.
conclusionThe microenvironment, modified by liver injury, increased HBSP RNA expression through splicing factor regulation, which in turn controlled hepatocyte chemokine synthesis. This feedback mechanism provides a novel insight into liver immunopathogenesis during HBV infection. Lay summary: Hepatitis B virus persists for decades in the liver of chronically infected patients. Immune escape is one of the main mechanisms developed by this virus to survive. Our study highlights how the crosstalk between virus and liver infected cells may contribute to this immune escape.
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