The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations.
The non-nucleoside reverse transcriptase inhibitor efavirenz stimulates replication of human immunodeficiency virus type 1 harboring certain non-nucleoside resistance mutations.
复制标题
非核苷逆转录酶抑制剂依非韦伦可刺激含有某些非核苷抗性突变的 1 型人类免疫缺陷病毒的复制。
DOI：
10.1016/j.virol.2010.03.018
复制
发表时间：
2010
期刊：
影响因子：
3.7
通讯作者：
Dykes,C
中科院分区：
文献类型：
--
作者：
Wang,J;Liang,H;Bacheler,L;Wu,H;Deriziotis,K;Demeter,LM;Dykes,C
我们测量了非核苷逆转录酶（RT）突变K101 E + G190 S对HIVNL 4 -3的复制适应性和EFV抗性的影响。K101 E + G190 S在EFV不存在的情况下降低了适应性，并增加了EFV抗性，与任一单一突变体相比。出乎意料的是，K101 E + G190 S在EFV存在下也比在其不存在下更有效地复制。将核苷抗性突变L74 V或M41 L + T215 Y添加到K101 E + G190 S改善了适应性并消除了EFV依赖的复制刺激。D10是一种含有M41 L + T215 Y和K101 E + G190 S的临床RT骨架，也证明了依赖于K101 E存在的EFV依赖性刺激。这些研究表明，非核苷类逆转录酶抑制剂可以刺激NNRTI耐药HIV-1的复制，而核苷耐药突变体可以消除这种刺激。EFV刺激NNRTI抗性突变体的能力可能有助于体内HIV-1突变体的选择。这些研究对核苷和非核苷联合治疗HIV-1具有重要意义。
We measured the effects of non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutations K101E+G190S, on replication fitness and EFV-resistance of HIVNL4-3. K101E+G190S reduced fitness in the absence of EFV and increased EFV resistance, compared to either single mutant. Unexpectedly, K101E+G190S also replicated more efficiently in the presence of EFV than in its absence. Addition of the nucleoside resistance mutations L74V or M41L+T215Y to K101E+G190S improved fitness and abolished EFV-dependent stimulation of replication. D10, a clinical RT backbone containing M41L+T215Y and K101E+G190S, also demonstrated EFV-dependent stimulation that was dependent on the presence of K101E. These studies demonstrate that non-nucleoside reverse transcriptase inhibitors can stimulate replication of NNRTI-resistant HIV-1 and that nucleoside-resistant mutants can abolish this stimulation. The ability of EFV to stimulate NNRTI-resistant mutants may contribute to the selection of HIV-1 mutants in vivo. These studies have important implications regarding the treatment of HIV-1 with combination nucleoside and non-nucleoside therapies.