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Host cell dependence of HIV-1 tissue culture drug selection patterns and resistance profiles.
Salomon H; Gu Z; Gao Q; Fang H; Wainberg M; McGill AIDS Centre, Lady
December 30, 1995
Natl Conf Hum Retroviruses Relat Infect (1st). 1993 Dec 12-16;:134.

Tissue culture selection of cloned recombinant HIV-1 (HXB2- D) in MT-4 cells in the presence of ddI led to the generation of viruses possessing about 5-fold resistance to this drug (EC50 of 74 micromolar vs 18 micromolar). Such viruses were cross-resistant to ddC (EC50 of 1.8 micromolar vs 0.35 micromolar), displayed 500-1000 fold resistance to 3TC, as previously described, and contained a mutation at codon 184 (meth val) of the pol gene. This mutation has now been demonstrated in the PBMC of 5 of 20 individuals treated with ddI for longer than 1 year and from whom ddI-resistant viruses have been isolated. Growth of a recombinant virus (HXB2-D184) containing this mutation in peripheral blood mononuclear cells (PBMC) and Jurkat cells yielded progeny that behaved as fully sensitive to both ddI and ddC, but remained resistant to 3TC (approximately 500 fold). In contrast, replication of this virus in cord blood lymphocytes (CBL) continued to result in low-level resistance to both ddI and ddC. Tissue culture selection protocols in PBMC, CBL and Jurkat cells involving HXB2-D replication in increasing concentrations of ddI failed to yield either phenotypically resistant particles or to amplify the 184 mutation. These findings further underscore the complex nature of HIV drug resistance, which may be cell type dependent both with regard to likelihood of selection of resistant variants as well as outcome of assays employed to document resistance among isolates previously shown to display this phenotype in other systems.

Cell Line Chromatography, High Pressure Liquid Deoxyadenine Nucleotides/*BIOSYNTHESIS Didanosine/*TOXICITY Human Mitochondria/DRUG EFFECTS ABSTRACT