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Journal of Virology, December 2009, p. 12535-12544, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01623-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1{alpha} and Small Heterodimer Partner Differentially Regulate Nuclear Receptor-Dependent Hepatitis B Virus Biosynthesis {triangledown}

Caitlin R. Ondracek,{dagger} Christel N. Rushing,{dagger} Vanessa C. Reese, Claudia E. Oropeza, and Alan McLachlan*

Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, Illinois 60612

Received 4 August 2009/ Accepted 21 September 2009

Hepatitis B virus (HBV) biosynthesis involves the transcription of the 3.5-kb viral pregenomic RNA, followed by its reverse transcription into viral DNA. Consequently, the modulation of viral transcription influences the level of virus production. Nuclear receptors are the only transcription factors known to support viral pregenomic RNA transcription and replication. The coactivator peroxisome proliferator-activated receptor {gamma} coactivator 1{alpha} (PGC1{alpha}) and corepressor small heterodimer partner (SHP) have central roles in regulating energy homeostasis in the liver by modulating the transcriptional activities of nuclear receptors. Therefore, the effect of PGC1{alpha} and SHP on HBV transcription and replication mediated by nuclear receptors was examined in the context of individual nuclear receptors in nonhepatoma cells and in hepatoma cells. This analysis indicated that viral replication mediated by hepatocyte nuclear factor 4{alpha}, retinoid X receptor {alpha} (RXR{alpha}) plus peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}), and estrogen-related receptor (ERR) displayed differential sensitivity to PGC1{alpha} activation and SHP inhibition. The effects of PGC1{alpha} and SHP on viral biosynthesis in the human hepatoma cell line Huh7 were similar to those observed in the nonhepatoma cells expressing ERR{alpha} and ERR{gamma}. This suggests that these nuclear receptors, potentially in combination with RXR{alpha} plus PPAR{alpha}, may have a major role in governing HBV transcription and replication in this cell line. Additionally, this functional approach may help to distinguish the transcription factors in various liver cells governing viral biosynthesis under a variety of physiologically relevant conditions.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, 909 South Wolcott Avenue, Chicago, IL 60612. Phone: (312) 355-0211. Fax: (312) 996-4890. E-mail: mclach{at}uic.edu

{triangledown} Published ahead of print on 30 September 2009.

{dagger} C.R.O. and C.N.R. contributed equally to this study.

Journal of Virology, December 2009, p. 12535-12544, Vol. 83, No. 23
0022-538X/09/$08.00+0     doi:10.1128/JVI.01623-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ondracek, C. R., Reese, V. C., Rushing, C. N., Oropeza, C. E., McLachlan, A. (2009). Distinct Regulation of Hepatitis B Virus Biosynthesis by Peroxisome Proliferator-Activated Receptor {gamma} Coactivator 1{alpha} and Small Heterodimer Partner in Human Hepatoma Cell Lines. J. Virol. 83: 12545-12551 [Abstract] [Full Text]  


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