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Journal of Virology, February 1999, p. 1239-1244, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mechanism of Suppression of Hepatitis B Virus Precore RNA Transcription by a Frequent Double Mutation

Jie Li, Victor E. Buckwold,dagger Man-wai Hon, and Jing-hsiung Ou*

Department of Molecular Microbiology and Immunology, University of Southern California School of Medicine, Los Angeles, California

Received 28 July 1998/Accepted 31 October 1998

A double mutation which converts nucleotide 1765 from A to T and nucleotide 1767 from G to A is frequently found in the hepatitis B virus (HBV) genome isolated from HBV patients with chronic hepatitis symptoms. This double mutation is located in the core promoter that controls the transcription of the precore RNA and the core RNA. In addition, this double mutation also resides in the X protein coding sequence, converting codon 130 from Lys to Met and codon 131 from Val to Ile. Previous studies indicate that this double mutation removes a nuclear receptor binding site in the core promoter, suppresses specifically precore RNA transcription, and enhances viral replication. In this study, we further investigated how this double mutation suppresses precore RNA transcription. We found that this double mutation not only removed the nuclear receptor binding site but also created an HNF1 transcription factor binding site. Further transfection studies using Huh7 hepatoma cells indicate that the removal of the nuclear receptor binding site has no effect on the transcription of HBV RNAs, the two-codon change in the X protein sequence suppresses the transcription of both precore and core RNAs, and the creation of the HNF1 binding site restores the core RNA level. Hence, the specific suppression of precore RNA transcription by this frequent double-nucleotide mutation is the combined result of multiple factors.

* Corresponding author. Mailing address: Department of Molecular Microbiology and Immunology, 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.

dagger Present address: Departmento de Biología Molecular, Centro de Biología Molecular "Severo Ochoa," Universidad Autónoma de Madrid, Cantoblanco Universidad, 28049 Madrid, Spain.

Journal of Virology, February 1999, p. 1239-1244, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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