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Journal of Virology, March 2001, p. 2900-2911, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2900-2911.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Nuclear Covalently Closed Circular Viral Genomic DNA in the Liver of Hepatocyte Nuclear Factor 1alpha -Null Hepatitis B Virus Transgenic Mice†

Anneke K. Raney,1 Carrie M. Eggers,1 Eric F. Kline,1 Luca G. Guidotti,2 Marco Pontoglio,3 Moshe Yaniv,3 and Alan McLachlan1,*

Department of Cell Biology1 and Department of Molecular and Experimental Medicine,2 The Scripps Research Institute, La Jolla, California 92037, and Unité des Virus Oncogènes, UA1644 du CNRS, Départment des Biotechnologies, Institut Pasteur, Paris, France3

Received 29 August 2000/Accepted 11 December 2000

The role of hepatocyte nuclear factor 1alpha (HNF1alpha ) in the regulation of hepatitis B virus (HBV) transcription and replication in vivo was investigated using a HNF1alpha -null HBV transgenic mouse model. HBV transcription was not measurably affected by the absence of the HNF1alpha transcription factor. However, intracellular viral replication intermediates were increased two- to fourfold in mice lacking functional HNF1alpha protein. The increase in encapsidated cytoplasmic replication intermediates in HNF1alpha -null HBV transgenic mice was associated with the appearance of nonencapsidated nuclear covalently closed circular (CCC) viral genomic DNA. Viral CCC DNA was not readily detected in HNF1alpha -expressing HBV transgenic mice. This indicates the synthesis of nuclear HBV CCC DNA, the proposed viral transcriptional template found in natural infection, is regulated either by subtle alterations in the levels of viral transcripts or by changes in the physiological state of the hepatocyte in this in vivo model of HBV replication.

* Corresponding author. Mailing address: Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8097. Fax: (858) 784-2513. E-mail: mclach{at}scripps.edu.

dagger Publication no. 13419-CB from The Scripps Research Institute.

Journal of Virology, March 2001, p. 2900-2911, Vol. 75, No. 6
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.6.2900-2911.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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