In vitro selection and analysis of human immunodeficiency virus type 1 resistant to derivatives of beta-2',3'-didehydro-2',3'-dideoxy-5-fluorocytidine.
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.
Hammond
Jennifer L
JL
Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
Parikh
Urvi M
UM
Koontz
Dianna L
DL
Schlueter-Wirtz
Susan
S
Chu
Chung K
CK
Bazmi
Hengameh Z
HZ
Schinazi
Raymond F
RF
Mellors
John W
JW
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
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D003570:Cytidine Triphosphate; D016047:Zalcitabine; D054303:HIV Reverse Transcriptase; C099405:dexelvucitabine