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Journal of Virology, June 2002, p. 5875-5881, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.5875-5881.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Regulation of Hepatocyte Nuclear Factor 1 Activity by Wild-Type and Mutant Hepatitis B Virus X Proteins

Jie Li,¹ Zhenming Xu,¹ Yanyan Zheng,¹ Deborah L. Johnson,² and Jing-hsiung Ou^1*

Department of Molecular Microbiology and Immunology, Keck School of Medicine,¹ Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California 90033²

Received 14 September 2001/ Accepted 14 March 2002

The hepatitis B virus (HBV) core promoter regulates the transcription of two related RNA products named precore RNA and core RNA. Previous studies indicate that a double-nucleotide mutation that occurs frequently during chronic HBV infection converts a nuclear receptor binding site in the core promoter to the binding site of the transcription factor hepatocyte nuclear factor-1 (HNF-1) and specifically suppresses the transcription of the precore RNA. This mutation also changes two codons in the overlapping X protein coding sequence. In this report, we demonstrate that the X protein and its mutant X^mt can physically bind to HNF-1 both in vitro and in vivo. Further analyses indicate that both X and X^mt can enhance the gene transactivation and the DNA binding activities of HNF-1. This finding demonstrates for the first time that the X protein can stimulate the DNA binding activity of a homeodomain transcription factor. Interestingly, while both X and X^mt can stimulate the HNF-1 activities, they differ in their effects: a smaller amount of X^mt is needed to generate greater transactivation and DNA binding activities of HNF-1. This functional difference between X and X^mt may have important implications in HBV pathogenesis and is apparently why they have different effects on the core promoter bearing the HNF-1 binding site.

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* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, 2011 Zonal Ave., HMR-401, Los Angeles, CA 90033. Phone: (323) 442-1720. Fax: (323) 442-1721. E-mail: jamesou{at}hsc.usc.edu.

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Journal of Virology, June 2002, p. 5875-5881, Vol. 76, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.12.5875-5881.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

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