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Journal of Virology, November 2007, p. 12061-12065, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00740-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Hepatitis B Virus Replication Is Associated with an HBx-Dependent Mitochondrion-Regulated Increase in Cytosolic Calcium Levels{triangledown}

Stephanie L. McClain,{dagger} Amy J. Clippinger,{dagger} Rebecca Lizzano, and Michael J. Bouchard*

Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102

Received 5 April 2007/ Accepted 1 August 2007

The nonstructural hepatitis B virus (HBV) protein HBx has an important role in HBV replication and in HBV-associated liver disease. Many activities have been linked to HBx expression; however, the molecular mechanisms underlying many of these activities are unknown. One proposed HBx function is the regulation of cytosolic calcium. We analyzed calcium levels in HepG2 cells that expressed HBx or replicating HBV, and we demonstrated that HBx, expressed in the absence of other HBV proteins or in the context of HBV replication, elevates cytosolic calcium. We linked this elevation of cytosolic calcium to the association of HBx with the mitochondrial permeability transition pore.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102. Phone: (215) 762-1898. Fax: (215) 762-4452. E-mail: michael.bouchard{at}drexelmed.edu

{triangledown} Published ahead of print on 15 August 2007.

{dagger} The first two authors contributed equally to this work.

Journal of Virology, November 2007, p. 12061-12065, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00740-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Clippinger, A. J., Gearhart, T. L., Bouchard, M. J. (2009). Hepatitis B Virus X Protein Modulates Apoptosis in Primary Rat Hepatocytes by Regulating both NF-{kappa}B and the Mitochondrial Permeability Transition Pore. J. Virol. 83: 4718-4731 [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]  


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