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Journal of Virology, July 2001, p. 6492-6497, Vol. 75, No. 14
McArdle Laboratory for Cancer Research,
University of Wisconsin Medical School, Madison, Wisconsin 53706
Received 13 February 2001/Accepted 25 April 2001
The process of hepadnavirus reverse transcription involves two
template switches during the synthesis of plus-strand DNA. The first
involves translocation of the plus-strand primer from its site of
generation, the 3' end of minus-strand DNA, to the complementary
sequence DR2, located near the 5' end of the minus-strand DNA. Plus
strands initiated from DR2 are extended to the 5' end of the
minus-strand DNA. At this point, the 3' end of the minus strand becomes
the template via the second template switch, a process called
circularization. Elongation of circularized plus-strand DNA generates
relaxed circular DNA. Although most virions contain relaxed circular
DNA, some contain duplex linear DNA. Duplex linear genomes are
synthesized when the plus-strand primer is used at the site of its
generation, the 3' end of the minus-strand template. This type of
synthesis is called in situ priming. Although in situ priming is
normally low, in some duck hepatitis B virus mutants this type of
priming is elevated. For example, mutations within the 3' end of the
minus-strand DNA can lead to increased levels of in situ priming. We
report here that these same mutations result in a second defect, a less
efficient template switch that circularizes the genome. Although it is
not clear how these mutations affect both steps in DNA replication, our
findings suggest a commonality in the mechanism of initiation of
plus-strand synthesis and the template switch that circularizes the genome.
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6492-6497.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Mutations That Increase In Situ Priming Also
Decrease Circularization for Duck Hepatitis B Virus
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Corresponding author. Mailing address: McArdle
Laboratory for Cancer Research, University of Wisconsin Medical School,
1400 University Ave., Madison, WI 53706. Phone: (608) 262-1260. Fax: (608) 262-2824. E-mail: loeb{at}oncology.wisc.edu.
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