L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness.
L74V increases the reverse transcriptase content of HIV-1 virions with non-nucleoside reverse transcriptase drug-resistant mutations L100I+K103N and K101E+G190S, which results in increased fitness.
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L74V 增加具有非核苷逆转录酶耐药突变 L100I K103N 和 K101E G190S 的 HIV-1 病毒粒子的逆转录酶含量，从而导致适应性增加。
DOI：
10.1099/vir.0.050914-0
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Dykes,Carrie
中科院分区：
文献类型：
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作者：
Wang,Jiong;Li,Dongge;Bambara,RobertA;Yang,Hongmei;Dykes,Carrie
HIV-1非核苷类逆转录酶抑制剂（NNRTI）耐药逆转录酶（RT）突变体的适应度与病毒粒子中RT的数量和RT的RNase H活性相关。我们希望了解继发的NNRTI耐药突变L100I和K101E以及核苷耐药突变L74V改变K103N和G190S病毒适应度的机制。与野生型、K103N和G190S相比，我们测量了突变型RTs在病毒粒子中的RT含量以及聚合和RNase H活性。我们发现L100I， K101E和L74V对K103N和G190S RTs的聚合和RNase H活性没有影响。然而，L100I和K101E降低了病毒粒子中的RT量，随后添加L74V使RT水平恢复到G190S或K103N单独时的水平。我们认为L100I、K101E和L74V引起的适应度变化源于它们对RT含量的影响。
The fitness of non-nucleoside reverse transcriptase inhibitor (NNRTI) drug-resistant reverse transcriptase (RT) mutants of HIV-1 correlates with the amount of RT in the virions and the RNase H activity of the RT. We wanted to understand the mechanism by which secondary NNRTI-resistance mutations, L100I and K101E, and the nucleoside resistance mutation, L74V, alter the fitness of K103N and G190S viruses. We measured the amount of RT in virions and the polymerization and RNase H activities of mutant RTs compared to wild-type, K103N and G190S. We found that L100I, K101E and L74V did not change the polymerization or RNase H activities of K103N or G190S RTs. However, L100I and K101E reduced the amount of RT in the virions and subsequent addition of L74V restored RT levels back to those of G190S or K103N alone. We conclude that fitness changes caused by L100I, K101E and L74V derive from their effects on RT content.