The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection
Open accessAbstract
BACKGROUND & AIMS The molecular biology of hepatitis B virus (HBV) has been extensively studied but the exact role of the hepatitis B X protein (HBx) in the context of natural HBV infections remains unknown. METHODS Primary human hepatocytes and differentiated HepaRG cells allowing conditional trans complementation of HBx were infected with wild type (HBV(wt)) or HBx deficient (HBV(x-)) HBV particles and establishment of HBV replication was followed. RESULTS We observed that cells inoculated with HBx-deficient HBV particles (HBV(x-)) did not lead to productive HBV infection contrary to cells inoculated with wild type HBV particles (HBV(wt)). Although equal amounts of nuclear covalently closed circular HBV-DNA (cccDNA) demonstrated comparable uptake and nuclear import, active transcription was only observed from HBV(wt) genomes. Trans-complementation of HBx was able to rescue transcription from the HBV(x-) genome and led to antigen and virion secretion, even weeks after infection. Constant expression of HBx was necessary to maintain HBV antigen expression and replication. Finally, we demonstrated that HBx is not packaged into virions during assembly but is expressed after infection within the new host cell to allow epigenetic control of HBV transcription from cccDNA. CONCLUSIONS Our results demonstrate that HBx is required to initiate and maintain HBV replication and highlight HBx as the key regulator during the natural infection process.
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Cites
Infection of a human hepatoma cell line by hepatitis B virus
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Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function
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Self-citationWoodchuck hepatitis virus X protein is required for viral infection in vivo
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Self-citationCalcium Signaling by HBx Protein in Hepatitis B Virus DNA Replication
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The woodchuck hepatitis virus X gene is important for establishment of virus infection in woodchucks
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Structural organization of the hepatitis B virus minichromosome
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Mechanisms of HBV-induced hepatocellular carcinoma
Levrero, M., & Zucman-Rossi, J. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.021 · Cited by 1,052
Self-citationSpecific and Nonhepatotoxic Degradation of Nuclear Hepatitis B Virus cccDNA
Lucifora, J., Xia, Y., Reisinger, F., Zhang, K., Stadler, D., Cheng, X., Sprinzl, M. F., Koppensteiner, H., Makowska, Z., Volz, T., et al. (2014) · Science · doi:10.1126/science.1243462 · Cited by 893
Self-citationA global scientific strategy to cure hepatitis B
Revill, P. A., Chisari, F. V., Block, J. M., Dandri, M., Gehring, A. J., Guo, H., Hu, J., Kramvis, A., Lampertico, P., Janssen, H. L. A., et al. (2019) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30119-0 · Cited by 508
Self-citationTargeting Hepatitis B Virus With CRISPR/Cas9
Seeger, C., & Sohn, J. A. (2014) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2014.68 · Cited by 294
Core protein: A pleiotropic keystone in the HBV lifecycle
Zlotnick, A., Venkatakrishnan, B., Tan, Z., Lewellyn, E., Turner, W., & Francis, S. (2015) · Antiviral Research · doi:10.1016/j.antiviral.2015.06.020 · Cited by 268
Metadata
- Authors
- Lucifora, J., Arzberger, S., Durantel, D., Belloni, L., Strubin, M., Levrero, M., Zoulim, F., Hantz, O., & Protzer, U.
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2011-11
- Volume
- 55
- Issue
- 5
- Pages
- 996-1003
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2043861742
- Cited by
- 481
- References
- 27
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Open access
- green
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- Lucifora, J., Arzberger, S., Durantel, D., Belloni, L., Strubin, M., Levrero, M., Zoulim, F., Hantz, O., & Protzer, U. (2011). Hepatitis B virus X protein is essential to initiate and maintain virus replication after infection. Journal of Hepatology. https://doi.org/10.1016/j.jhep.2011.02.015
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