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Journal of Virology, November 2007, p. 11577-11584, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01414-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The Topology of Hepatitis B Virus Pregenomic RNA Promotes Its Replication{triangledown}

Teresa M. Abraham1,2 and Daniel D. Loeb1*

McArdle Laboratory for Cancer Research,1 Program in Cellular and Molecular Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 537062

Received 28 June 2007/ Accepted 8 August 2007

Previous analysis of hepatitis B virus (HBV) indicated base pairing between two cis-acting sequences, the 5' half of the upper stem of {varepsilon} and {phi}, contributes to the synthesis of minus-strand DNA. Our goal was to identify other cis-acting sequences on the pregenomic RNA (pgRNA) involved in the synthesis of minus-strand DNA. We found that large portions of the pgRNA could be deleted or substituted without an appreciable decrease in the level of minus-strand DNA synthesized, indicating that most of the pgRNA is dispensable and that a specific size of the pgRNA is not required for this process. Our results indicated that the cis-acting sequences for the synthesis of minus-strand DNA are present near the 5' and 3' ends of the pgRNA. In addition, we found that the first-strand template switch could be directed to a new location when a 72-nucleotide (nt) fragment, which contained the cis-acting sequences present near the 3' end of the pgRNA, was introduced at that location. Within this 72-nt region, we uncovered two new cis-acting sequences, which flank the acceptor site. We show that one of these sequences, named {omega} and located 3' of the acceptor site, base pairs with {phi} to contribute to the synthesis of minus-strand DNA. Thus, base pairing between three cis-acting elements (5' half of the upper stem of {varepsilon}, {phi}, and {omega}) are necessary for the synthesis of HBV minus-strand DNA. We propose that this topology of pgRNA facilitates first-strand template switch and/or the initiation of synthesis of minus-strand DNA.

* Corresponding author. Mailing address: McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706. Phone: (608) 262-1260. Fax: (608) 262-2824. E-mail: loeb{at}oncology.wisc.edu

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

Journal of Virology, November 2007, p. 11577-11584, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.01414-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wang, H., Kim, S., Ryu, W.-S. (2009). DDX3 DEAD-Box RNA Helicase Inhibits Hepatitis B Virus Reverse Transcription by Incorporation into Nucleocapsids. J. Virol. 83: 5815-5824 [Abstract] [Full Text]  
  • Nguyen, D. H., Hu, J. (2008). Reverse Transcriptase- and RNA Packaging Signal-Dependent Incorporation of APOBEC3G into Hepatitis B Virus Nucleocapsids. J. Virol. 82: 6852-6861 [Abstract] [Full Text]  


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