ArticleProceedings of the National Academy of Sciences of the United States of America2012
Hepatitis B virus X protein targets Bcl-2 proteins to increase intracellular calcium, required for virus replication and cell death induction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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The trial behind it
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
52 citing papers in PubMed, 93 citations in OpenAlex.
- Effect of Hepatitis B virus X T118N mutant protein in HepG2 cell cycle and apoptosis regulation.Molecular biology reports · 2026Article
- HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control.Nature communications · 2026Article
- SADS-CoV NS3 induces apoptosis by blocking the formation of Bcl-xL-BAK complex.Journal of virology · 2026Article
- Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.Hepatology (Baltimore, Md.) · 2025Article
- The crucial role of intercellular calcium wave propagation triggered by influenza A virus in promoting infection.Cell communication and signaling : CCS · 2025Article
- Hepatitis B virus genotypes A1 and A2 have distinct replication phenotypes due to polymorphisms in the HBx gene.PLoS pathogens · 2025Article
- Immunoinformatics and Evaluation of Peptide Vaccines Derived from Global Hepatitis B Viral HBx and HBc Proteins Critical for Covalently Closed Circular DNA Integrity.Microorganisms · 2023Article
- System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.International journal of molecular sciences · 2023Article
- Canonical and Divergent N-Terminal HBx Isoform Proteins Unveiled: Characteristics and Roles during HBV Replication.Biomedicines · 2021Article
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- The Role of Bcl-xL Protein in Viral Infections.International journal of molecular sciences · 2021Review
- Risk Factors and Biomarkers for Chronic Hepatitis B Associated Hepatocellular Carcinoma.International journal of molecular sciences · 2021Review
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- HBx represses WDR77 to enhance HBV replication by DDB1-mediated WDR77 degradation in the liver.Theranostics · 2021Article
- Alpha-fetoprotein accelerates the progression of hepatocellular carcinoma by promoting Bcl-2 gene expression through an RA-RAR signalling pathway.Journal of cellular and molecular medicine · 2020Article
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- Review
- Structural and functional analyses of hepatitis B virus X protein BH3-like domain and Bcl-xL interaction.Nature communications · 2019Article
- Hepatitis B virus X protein enhances hepatocarcinogenesis by depressing the targeting ofCancer biology & medicine · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Infection with the hepatitis B virus (HBV) promotes the development of hepatitis, cirrhosis, and hepatocellular carcinoma (HCC) and is a leading cause of morbidity and mortality worldwide. HBV X protein (HBx) is an important effector for HBV pathogenesis, but its cellular targets and acting mechanisms remain elusive. We show here that HBx interacts with the anti-apoptotic proteins Bcl-2 and Bcl-xL through a Bcl-2 homology 3 (BH3)-like motif in mammalian cells. Importantly, mutations in the BH3-like motif that prevent HBx binding to Bcl-2 and Bcl-xL abrogate cytosolic calcium elevation and cell death induced by HBx expression in hepatocytes and severely impair HBV viral replication, which can be substantially rescued by restoring cytosolic calcium. These results suggest that HBx binding to Bcl-2 family members and subsequent elevation of cytosolic calcium are important for HBV viral replication. Consistently, RNAi knockdown of Bcl-2 or Bcl-xL results in reduced calcium elevation by HBx and decreased viral replication in hepatocytes. Our results suggest that HBx targets Bcl-2 proteins through its BH3-like motif to promote cytosolic calcium elevation, cell death, and viral replication during HBV pathogenesis, which presents an excellent therapeutic intervention point in treating patients with chronic HBV.
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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.