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Antimicrobial Agents and Chemotherapy, September 2005, p. 3930-3932, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3930-3932.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

In Vitro Selection and Analysis of Human Immunodeficiency Virus Type 1 Resistant to Derivatives of ß-2',3'-Didehydro-2',3'-Dideoxy-5-Fluorocytidine

Jennifer L. Hammond,1 Urvi M. Parikh,1 Dianna L. Koontz,1 Susan Schlueter-Wirtz,2 Chung K. Chu,3 Hengameh Z. Bazmi,1 Raymond F. Schinazi,2 and John W. Mellors1*

Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,1 Department of Pediatrics, Emory University School of Medicine, and the Georgia VA Research Center on AIDS and HIV Infection, Veterans Affair Medical Center, Decatur, Georgia 30033,2 College of Pharmacy, The University of Georgia, Athens, Georgia 306023

Received 19 January 2005/ Returned for modification 10 March 2005/ Accepted 15 June 2005

Serial passage of human immunodeficiency virus type 1 in MT-2 cells in increasing concentrations of the D- and L-enantiomers of ß-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine (d4FC) resulted in the selection of viral variants with reverse transcriptase substitutions M184I or M184V for L-d4FC and I63L, K65R, K70N, K70E, or R172K for D-d4FC. Phenotypic analysis of site-directed mutants defined the role of these mutations in reducing susceptibility to L- or D-d4FC.

* Corresponding author. Mailing address: 818 Scaife Hall, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261. Phone: (412) 624-8512. Fax: (412) 383-7982. E-mail: mellors{at}dom.pitt.edu.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3930-3932, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3930-3932.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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