Sheehy N, Desselberger U
Regional Virus Laboratory, East Birmingham Hospital, U.K.
J Gen Virol. 1993 Feb;74 ( Pt 2):223-8. doi: 10.1099/0022-1317-74-2-223.
Sequential isolates of human immunodeficiency virus type 1 (HIV-1) were obtained from patients with AIDS on short and long term treatment with zidovudine (3'-azido-3'-deoxythymidine; AZT). The isolates were tested for resistance to zidovudine by monitoring the inhibition of syncytium formation, HIV-1-specific immunofluorescence and p24 production in C8166 cells. The reverse transcriptase (RT) genes of zidovudine-sensitive (< 1 microM) and -resistant (10 to 15 microM) strains were amplified using the polymerase chain reaction and the products were sequenced directly. The predicted amino acid sequences of the RTs of zidovudine-sensitive and -resistant isolates showed 95 to 97% identity to the corresponding sequence of HIV-1SF2 which was used as a reference. Amino acid changes at positions 41, 67, 70, 215 and 219 which are known to be associated with zidovudine resistance were present in some, but not all isolates exhibiting zidovudine resistance in vitro. This indicates that mutations in the RT of HIV-1, other than those already identified, may be involved in conferring resistance to zidovudine.
从接受齐多夫定（3'-叠氮-3'-脱氧胸苷；AZT）短期和长期治疗的艾滋病患者中获取了1型人类免疫缺陷病毒（HIV-1）的连续分离株。通过监测C8166细胞中合胞体形成的抑制、HIV-1特异性免疫荧光和p24产生，对分离株进行了齐多夫定耐药性检测。使用聚合酶链反应扩增齐多夫定敏感（<1 microM）和耐药（10至15 microM）菌株的逆转录酶（RT）基因，并直接对产物进行测序。齐多夫定敏感和耐药分离株RT的预测氨基酸序列与用作参考的HIV-1SF2相应序列显示出95%至97%的同一性。在一些但并非所有体外表现出齐多夫定耐药性的分离株中，存在已知与齐多夫定耐药性相关的第41、67、70、215和219位氨基酸变化。这表明HIV-1 RT中的突变，除了那些已确定的突变外，可能参与赋予对齐多夫定的耐药性。
