title: In vitro selection and analysis of human immunodeficiency virus type 1 resistant to derivatives of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine.
abstract: Serial passage of human immunodeficiency virus type 1 in MT-2 cells in increasing concentrations of the d- and l-enantiomers of beta-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.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hammond
authors.forename: Urvi M
authors.initials: UM
authors.lastname: Parikh
authors.forename: Dianna L
authors.initials: DL
authors.lastname: Koontz
authors.forename: Susan
authors.initials: S
authors.lastname: Schlueter-Wirtz
authors.forename: Chung K
authors.initials: CK
authors.lastname: Chu
authors.forename: Hengameh Z
authors.initials: HZ
authors.lastname: Bazmi
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Schinazi
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D002460:Cell Line; D003570:Cytidine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D016047:Zalcitabine / Q000031:analogs & derivatives
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D003570:Cytidine Triphosphate; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase; C099405:dexelvucitabine