Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure
Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure
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DOI：
10.1073/pnas.93.12.6106
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发表时间：
1996-06-11
影响因子：
11.1
通讯作者：
Richman, DD
中科院分区：
文献类型：
--
作者：
Moutouh, L;Corbeil, J;Richman, DD
研究了重组在HIV-1对多种药物耐药性发展中的潜在贡献。两种不同的病毒，一种对一种蛋白酶抑制剂(SC-52151)高度抵抗，另一种对齐多夫定高度抵抗，被用来共同感染培养中的T淋巴母细胞。病毒的基因类型可以通过对每种药物产生耐药性的四个突变和每种亲本病毒特有的其他序列差异来区分。从混合感染中恢复的子代病毒粒子在齐多夫定和SC-52151存在和不存在的情况下传代。双抗突变体在选择条件下迅速出现，这些病毒是遗传重组体。这些结果强调，基因重组可能导致高水平的多药耐药，在艾滋病毒感染的化疗策略中必须考虑这一过程。
The potential contribution of recombination to the development of HIV-1 resistance to multiple drugs was investigated. Two distinct viruses, one highly resistant to a protease inhibitor (SC-52151) and the other highly resistant to zidovudine, were used to coinfect T lymphoblastoid cells in culture. The viral genotypes could be distinguished by four mutations conferring drug resistance to each drug and by other sequence differences specific for each parental virus. Progeny virions recovered from mixed infection were passaged in the presence and absence of both zidovudine and SC-52151. Dually resistant mutants emerged rapidly under selective conditions, and these viruses were genetic recombinants. These results emphasize that genetic recombination could contribute to high-level multiple-drug resistance and that this process must be considered in chemotherapeutic strategies for HIV infection.