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Journal of Virology, August 2002, p. 7560-7570, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7560-7570.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mutation of the Catalytic Domain of the Foamy Virus Reverse Transcriptase Leads to Loss of Processivity and Infectivity

Carolyn S. Rinke,1,2 Paul L. Boyer,3 Mark D. Sullivan,1,{dagger} Stephen H. Hughes,3 and Maxine L. Linial1,2*

Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,1 Department of Microbiology, University of Washington, Seattle, Washington 98195,2 ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 217023

Received 22 August 2001/ Accepted 23 April 2002

Foamy virus (FV) replication is resistant to most nucleoside analog reverse transcriptase (RT) inhibitors. In an attempt to create a 2',3'-dideoxy-3'-thiacytidine (3TC)-sensitive virus, the second residue in the highly conserved YXDD motif of simian foamy virus-chimpanzee (human isolate) [SFVcpz(hu)] RT was changed from Val (V) to Met (M). Unexpectedly, the resultant virus, SFVcpz(hu) RT-V313M, replicated poorly, and Met rapidly reverted to Val. Despite the presence of approximately 50% of wild-type RT activity in RT-V313M virions, full-length DNA products were not detected in transfected cells. Using purified recombinant enzymes, we found that the wild-type FV RT is significantly more processive than human immunodeficiency virus type 1 RT. However, the V313M mutant has about 40% of the wild-type level of FV RT activity and has a lower processivity than the wild-type FV enzyme. The V313M mutant RT is also relatively resistant to 3TC. These results suggest that the decrease in RT activity and processivity of FV RT-V313M prevents completion of reverse transcription and greatly diminishes viral replication.

* Corresponding author. Mailing address: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109. Phone: (206) 667-4442. Fax: (206) 667-5939. E-mail: mlinial{at}fhcrc.org.

{dagger} Present address: University of Washington School of Medicine, Seattle, WA 98195.

Journal of Virology, August 2002, p. 7560-7570, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7560-7570.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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