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Journal of Virology, February 2009, p. 2029-2033, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01349-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Template Usage Is Responsible for the Preferential Acquisition of the K65R Reverse Transcriptase Mutation in Subtype C Variants of Human Immunodeficiency Virus Type 1{triangledown} ,{dagger}

Dimitrios Coutsinos,1,2,3 Cédric F. Invernizzi,1,3 Hongtao Xu,1 Daniela Moisi,1 Maureen Oliveira,1 Bluma G. Brenner,1,2,3 and Mark A. Wainberg1,2,3*

McGill University AIDS Center,1 Departments of Microbiology and Immunology,2 Medicine, McGill University, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, 3755 Côte-Ste-Catherine, Montréal, QC H3T 1E2, Canada3

Received 27 June 2008/ Accepted 27 November 2008

We propose that a nucleotide template-based mechanism facilitates the acquisition of the K65R mutation in subtype C human immunodeficiency virus type 1 (HIV-1). Different patterns of DNA synthesis were observed using DNA templates from viruses of subtype B or C origin. When subtype C reverse transcriptase (RT) was employed to synthesize DNA from subtype C DNA templates, preferential pausing was seen at the nucleotide position responsible for the AAG-to-AGG K65R mutation. This did not occur when the subtype B RT and template were used. Template factors can therefore increase the probability of K65R development in subtype C HIV-1.

* Corresponding author. Mailing address: Jewish General Hospital-Lady Davis, McGill AIDS Center, 3755 Chemin Côte-Ste-Catherine, Montréal, QC H3T 1E2, Canada. Phone: (514) 340-8307. Fax: (514) 340-7537. E-mail: mark.wainberg{at}mcgill.ca

{triangledown} Published ahead of print on 10 December 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, February 2009, p. 2029-2033, Vol. 83, No. 4
0022-538X/09/$08.00+0     doi:10.1128/JVI.01349-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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