This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Tang, H.
Right arrow Articles by Murakami, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, H.
Right arrow Articles by Murakami, S.

 Previous Article  |  Next Article 

Journal of Virology, May 2005, p. 5548-5556, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5548-5556.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Transcriptional Transactivation Function of HBx Protein Is Important for Its Augmentation Role in Hepatitis B Virus Replication

Hong Tang,1 Luvsanjav Delgermaa,2 Feijun Huang,3 Naoki Oishi,2 Li Liu,1 Fang He,1 Liansan Zhao,1 and Seishi Murakami2*

Division of Biotherapy of Infectious Diseases, State Key Laboratory of Biotherapy of China, and Department of Infectious Diseases, West China Hospital of Sichuan University,1 Department of Forensic Pathology, Medical School of Basic and Forensic Sciences, Sichuan University, Chengdu, Sichuan, People's Republic of China,3 Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan2

Received 9 August 2004/ Accepted 15 December 2004

The role and functional domain of hepatitis B virus (HBV) X protein (HBx) in regulating HBV transcription and replication were investigated with a transient transfection system in the human hepatoma cell line HepG2 using wild-type or HBx-minus HBV genome constructs and a series of deletion or mutation HBx expression plasmids. We show here that HBx has augmentation effects on HBV transcription and replication as a HBV mutant genome with defective X gene led to decreased levels of 3.5-kb HBV RNA and HBV replication intermediates and that these decreases can be restored by either transient ectopic expression of HBx or a stable HBx expression cell line. The C-terminal two-thirds (amino acids [aa] 51 to 154), which contain the transactivation domain, is required for this function of HBx; the N-terminal one-third (aa 1 to 50) is not required. Using the alanine scanning mutagenesis strategy, we demonstrated that the regions between aa 52 to 65 and 88 to 154 are important for the augmentation function of HBx in HBV replication. By the luciferase reporter gene analysis, we found that the transactivation and coactivation activities of HBx coincide well with its augmentation function in HBV transcription and replication. These results suggest that HBx has an important role in stimulating HBV transcription and replication and that the transcriptional transactivation function of HBx may be critical for its augmentation effect on HBV replication.

* Corresponding author. Mailing address: Department of Molecular Oncology, Cancer Research Institute, Kanazawa University, Takara-machi 13-1, Kanazawa 920-0934, Japan. Phone: 81-76-265-2731. Fax: 81-76-234-4501. E-mail: semuraka{at}kenroku.kanazawa-u.ac.jp.

Journal of Virology, May 2005, p. 5548-5556, Vol. 79, No. 9
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.9.5548-5556.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Belloni, L., Pollicino, T., De Nicola, F., Guerrieri, F., Raffa, G., Fanciulli, M., Raimondo, G., Levrero, M. (2009). Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc. Natl. Acad. Sci. USA 106: 19975-19979 [Abstract] [Full Text]  
  • Cha, M.-Y., Ryu, D.-K., Jung, H.-S., Chang, H.-E., Ryu, W.-S. (2009). Stimulation of hepatitis B virus genome replication by HBx is linked to both nuclear and cytoplasmic HBx expression. J. Gen. Virol. 90: 978-986 [Abstract] [Full Text]  
  • Clippinger, A. J., Bouchard, M. J. (2008). Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential. J. Virol. 82: 6798-6811 [Abstract] [Full Text]  
  • Wen, Y., Golubkov, V. S., Strongin, A. Y., Jiang, W., Reed, J. C. (2008). Interaction of Hepatitis B Viral Oncoprotein with Cellular Target HBXIP Dysregulates Centrosome Dynamics and Mitotic Spindle Formation. J. Biol. Chem. 283: 2793-2803 [Abstract] [Full Text]  
  • Keasler, V. V., Hodgson, A. J., Madden, C. R., Slagle, B. L. (2007). Enhancement of Hepatitis B Virus Replication by the Regulatory X Protein In Vitro and In Vivo. J. Virol. 81: 2656-2662 [Abstract] [Full Text]  
  • Cougot, D., Wu, Y., Cairo, S., Caramel, J., Renard, C.-A., Levy, L., Buendia, M. A., Neuveut, C. (2007). The Hepatitis B Virus X Protein Functionally Interacts with CREB-binding Protein/p300 in the Regulation of CREB-mediated Transcription. J. Biol. Chem. 282: 4277-4287 [Abstract] [Full Text]  
  • Fujiwara, K., Tanaka, Y., Paulon, E., Orito, E., Sugiyama, M., Ito, K., Ueda, R., Mizokami, M., Naoumov, N. V. (2005). Novel Type of Hepatitis B Virus Mutation: Replacement Mutation Involving a Hepatocyte Nuclear Factor 1 Binding Site Tandem Repeat in Chronic Hepatitis B Virus Genotype E. J. Virol. 79: 14404-14410 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»