The "Connection" Between HIV Drug Resistance and RNase H.

The "Connection" Between HIV Drug Resistance and RNase H.
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DOI:
10.3390/v2071476
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发表时间:
2010-07-01
期刊:
Viruses
影响因子:
--
通讯作者:
Pathak VK
Pathak VK
中科院分区:
其他
文献类型:
--
作者:
Delviks-Frankenberry KA;Nikolenko GN;Pathak VK

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目前,核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)是两类被批准用于治疗HIV-1感染的抗逆转录病毒药物。由于NRTIs和NNRTIs都靶向逆转录酶(RT)的聚合酶(pol)结构域,因此大多数耐药基因型分析仅限于RT的前1000个氨基酸。然而,最近的研究表明,RT的C端结构域(特别是连接亚结构域和RNA酶H结构域)突变也会增加对NRTIs和NNRTIs的耐药性。在这篇综述中,我们将提出的潜在机制,在RT的C-末端结构域的突变影响NRTI和NNRTI的敏感性,总结了这些区域的RT的突变的患病率确定的日期,并讨论其重要性的临床耐药。
Currently, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) are two classes of antiretroviral agents that are approved for treatment of HIV-1 infection. Since both NRTIs and NNRTIs target the polymerase (pol) domain of reverse transcriptase (RT), most genotypic analysis for drug resistance is limited to the first ∼300 amino acids of RT. However, recent studies have demonstrated that mutations in the C-terminal domain of RT, specifically the connection subdomain and RNase H domain, can also increase resistance to both NRTIs and NNRTIs. In this review we will present the potential mechanisms by which mutations in the C-terminal domain of RT influence NRTI and NNRTI susceptibility, summarize the prevalence of the mutations in these regions of RT identified to date, and discuss their importance to clinical drug resistance.
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