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Journal of Virology, October 1999, p. 8441-8447, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Altering the Intracellular Environment Increases the Frequency of Tandem Repeat Deletion during Moloney Murine Leukemia Virus Reverse Transcription

Julie K. Pfeiffer, Robert S. Topping,dagger Nam-Hee Shin, and Alice Telesnitsky*

Department of Microbiology and Immunology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan 48109-0620

Received 19 March 1999/Accepted 2 July 1999

During retroviral DNA synthesis reverse transcriptase frequently performs nonrequired template switches that can lead to genetic rearrangements or recombination. It has been postulated that template switching occurs after pauses in the action of reverse transcriptase. Hence factors which affect pausing, such as polymerization rate, may affect the frequency of template switching. To address the hypothesis that increasing the time required to complete reverse transcription increases the frequency of template switching, we established conditions that lengthened the time required to complete a single round of intracellular Moloney murine leukemia virus reverse transcription approximately threefold. Under these conditions, which resulted from intracellular nucleotide pool imbalances generated with hydroxyurea, we examined template switching frequency using a lacZ-based tandem repeat deletion assay. We observed that the frequency of deletion during reverse transcription in hydroxyurea-treated cells was approximately threefold higher than that in untreated control cells. These findings suggest that rates of retroviral recombination may vary when the intracellular environment is altered.

* Corresponding author. Mailing address: University of Michigan Medical School, 5641 Medical Sciences Bldg. II, Ann Arbor, MI 48109-0620. Phone: (734) 936-6466. Fax: (734) 764-3562. E-mail: ateles{at}umich.edu.

dagger Present address: Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48105.

Journal of Virology, October 1999, p. 8441-8447, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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