The implications of resistance to antiviral agents for herpesvirus drug targets and drug therapy.
The implications of resistance to antiviral agents for herpesvirus drug targets and drug therapy.
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DOI：
10.1016/0166-3542(91)90010-o
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发表时间：
1991-05
影响因子：
7.6
通讯作者：
D. Coen
中科院分区：
文献类型：
--
作者：
D. Coen
抗病毒药物耐药性是治疗包括单纯疱疹病毒（HSV）和人类巨细胞病毒（CMV）在内的多种病毒的临床重要性日益增加的一个领域。对这些疱疹病毒的研究说明了耐药性研究的价值。药物机制的新方面，例如有助于更昔洛韦磷酸化的 CMV 基因产物，可以通过耐药突变来识别。药物靶标，例如参与药物识别的 HSV DNA 聚合酶，可以通过耐药突变的测序来剖析，这可以指出替代的治疗策略。对动物模型和患者群体中病毒突变体的分析有助于评估病毒蛋白（例如 HSV 胸苷激酶和核糖核苷酸还原酶）作为药物靶点的价值以及耐药突变体的致病潜力。此类研究揭示了赋予耐药性的广泛改变，并强调了病毒异质群体在耐药性和发病机制中的重要性以及开发替代疗法的必要性。
Antiviral drug resistance is an area of increasing clinical importance in treatment of a number of viruses including herpes simplex virus (HSV) and human cytomegalovirus (CMV). Work with these herpesviruses illustrates the value of studies of drug resistance. Novel aspects of drug mechanisms, such as a CMV gene product that contributes to ganciclovir phosphorylation, can be identified via drug resistance mutations. Drug targets such as the HSV DNA polymerase that are involved in drug recognition can be dissected by sequencing of drug-resistance mutations, which can point to alternate therapeutic strategies. Analysis of virus mutants in animal models and in patient populations can help assess the value of viral proteins such as the HSV thymidine kinase and ribonucleotide reductase as drug targets and the pathogenic potential of drug resistant mutants. Such studies reveal a broad spectrum of alterations conferring resistance and emphasize the importance of heterogeneous populations of virus in resistance and pathogenesis and the need to develop alternate therapies.