In Vitro Selection and Analysis of Human Immunodeficiency Virus Type 1 Resistant to Derivatives of β-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 β-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.

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