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The Same Mutation That Encodes Low-level Human Immunodeficiency Virus Type 1 Resistance To 2',3'-dideoxyinosine And 2',3'-dideoxycytidine Confers High-level Resistance To The (-) Enantiomer Of 2',3'-dideoxy-3'-thiacytidine

Q Gao, Z Gu, M A Parniak, J Cameron, N Cammack, C Boucher, M A Wainberg

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Variants of human immunodeficiency virus type 1 that display 500- to 1,000-fold resistance to the (-) enantiomer of 2'-deoxy-3'-thiacytidine and approximately 4- to 8-fold resistance to 2',3'-dideoxycytidine and 2',3'-dideoxyinosine have been generated through in vitro selection with the former compound. The polymerase regions of several of these resistant viruses shared a codon alteration at site 184 (ATG-->GTG; methionine-->valine), a mutation previously associated with low-level resistance to 2',3'-dideoxycytidine. The biological relevance of this mutation for the (-) enantiomer of 2'-deoxy-3'-thiacytidine was confirmed by site-directed mutagenesis with the HXB2-D clone of human immunodeficiency virus type 1.