Effects of mutations in the connection and RNase H domains of HIV-1 reverse transcriptase on drug susceptibility.
Effects of mutations in the connection and RNase H domains of HIV-1 reverse transcriptase on drug susceptibility.
复制标题
HIV-1 逆转录酶的连接和 RNase H 结构域突变对药物敏感性的影响。
作者：
M. Ehteshami;M. Götte
Despite the success in the development of antiretroviral therapy, the emergence of drug resistance remains an important factor that can undermine the benefits of treatment. The vast majority of well-described resistance-associated mutations are clustered around the binding site for a given inhibitor. However, mutations that are observed at considerable distance from this location can likewise affect drug susceptibility. Treatment-associated mutations in the C-terminal region of HIV-1 reverse transcriptase provide a recently surfaced example in this regard. In this review, we discuss the potential clinical significance of these mutations and underlying molecular mechanisms. Routine resistance testing does not usually include the C-terminal region of HIV-1 reverse transcriptase. However, previous studies have shown that mutations in this region can reduce susceptibility to both nucleoside and nonnucleoside reverse transcriptase inhibitors. The prevalence of some of these mutations can be as high as reported for several classic resistance mutations in HIV-1 reverse transcriptase. Biochemical studies provided plausible mechanisms that help to explain how certain C-terminal mutations can contribute to alterations in drug susceptibility and viral replication capacity. Overall, the available data warrant further investigation on the impact of C-terminal mutations in combination with classic resistance-associated mutations, on changes in viral load, and response to treatment with different classes of reverse transcriptase inhibitors.
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使用瞬态动力学分析探讨 HIV-1 逆转录酶介导的 AZT 耐药的分子机制。
DOI：
10.1021/bi034435l
发表时间：
2003
期刊：
Biochemistry.
影响因子：
--
作者：
Ray,AdrianS;Murakami,Eisuke;Basavapathruni,Aravind;Vaccaro,JosephA;Ulrich,Dagny;Chu,ChungK;Schinazi,RaymondF;Anderson,KarenS
通讯作者：
Anderson,KarenS
影响因子：
56.9
作者：
Huang, HF;Chopra, R;Harrison, SC
通讯作者：
Harrison, SC
影响因子：
56.9
作者：
KOHLSTAEDT, LA;WANG, J;STEITZ, TA
通讯作者：
STEITZ, TA
影响因子：
5.6
作者：
Gao, HQ;Boyer, PL;Hughes, SH
通讯作者：
Hughes, SH
影响因子：
5
作者：
Sluis-Cremer, Nicolas;Tachedjian, Gilda
通讯作者：
Tachedjian, Gilda