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 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.