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Antimicrobial Agents and Chemotherapy, November 2009, p. 4667-4672, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00800-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Recombinant Reverse Transcriptase Enzymes Containing the G190A and Y181C Resistance Mutations Remain Sensitive to Etravirine{triangledown}

Hongtao Xu,1 Yudong Quan,1 Bluma G. Brenner,1 Tamara Bar-Magen,1 Maureen Oliveira,1 Susan M. Schader,1,2 and Mark A. Wainberg1,2*

McGill University AIDS Centre, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada,1 Department of Microbiology and Immunology, McGill University, Montreal, Quebec, Canada2

Received 16 June 2009/ Returned for modification 27 July 2009/ Accepted 13 August 2009

Etravirine (ETR) is a second-generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) active against common human immunodeficiency virus type 1 (HIV-1) drug-resistant strains. This study was designed to determine the extent to which each of the Y181C or G190A mutations in RT might confer resistance to ETR and other members of the NNRTI family of drugs. Recombinant HIV-1 RT enzymes containing either the Y181C or the G190A mutation, or both mutations in tandem, were purified. Both RNA- and DNA-dependent DNA polymerase assays were performed in order to determine the extent to which each of these mutations might confer resistance in cell-free biochemical assays against each of ETR, efavirenz, and nevirapine. Both the biochemical and the cell-based phenotypic assays confirmed the susceptibility of G190A-containing enzymes and viruses to ETR. The results of this study indicate that the G190A mutation is not associated with resistance to ETR.

* Corresponding author. Mailing address: McGill University AIDS Centre, Jewish General Hospital, 3755 Cote Ste. Catherine Rd., Montreal, Quebec, Canada H3T 1E2. Phone: (514) 340-8260. Fax: (514) 340-7537. E-mail: mark.wainberg{at}mcgill.ca

{triangledown} Published ahead of print on 24 August 2009.

Antimicrobial Agents and Chemotherapy, November 2009, p. 4667-4672, Vol. 53, No. 11
0066-4804/09/$08.00+0     doi:10.1128/AAC.00800-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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