DRUG RESISTANCE IN HUMAN CYTOMEGALOVIRUS

人类巨细胞病毒的耐药性

• 批准号: 6188756
• 负责人: Sunwen Chou
• 金额: $ 3.15万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188756
• 关键词: AIDS; Herpesviridae disease; antiviral agents; artificial immunosuppression; clinical research; cytomegalovirus; diagnosis design /evaluation; drug resistance; gene mutation; genetic markers; human subject; immunodeficiency; rapid diagnosis; virus genetics

DESCRIPTION (Adapted from the Investigator's Abstract): This international collaboration is intended to improve the genetic characterization of drug resistance in human cytomegalovirus (CMV). In subjects with AIDS or other long term immunosuppression, CMV disease such as retinitis tends to be a relapsing condition that eventually progresses despite maintenance antiviral therapy. At present it is not clear how often disease progression is due to host or pharmacokinetic factors and how often it is due to mutations in CMV that cause drug resistance. The principal investigator and collaborator, working with drug-resistant isolates from their respective geographic sites, have identified many of the mutations in the UL97 phosphotransferase and DNA polymerase (Pol) genes of CMV that are so far known to be involved in drug resistance. The UL97 mutations that confer ganciclovir resistance are now fairly well defined, but resistance mutations in Pol, which have the potential to confer multi-drug resistance, are less well studied. The evolution of drug resistance mutations in treated subjects, and the associated changes in viral load and phenotype at various body sites, need to be better defined to guide clinical practice. The proposed contribution of serial specimens, isolates and diagnostic techniques from an established referral lab in Italy should result in an earlier answer to several important remaining questions. The specific aims of this collaboration are: 1. Monitor immunocompromised patients with CMV disease for clinical and virologic variables that predict drug resistance, and select specimens for detailed analysis of viral drug resistance markers. 2. Develop improved methods for the rapid phenotypic assay of drug resistance suitable for use in monitoring a course of antiviral therapy. 3. Genetically characterize CMV isolates form patients undergoing antiviral therapy, as to variability of the viral population within and between different body sites, the presence of mutations that confer drug resistance, and the biological properties of mutant viruses.

描述(改编自《调查者摘要》)：这个国际 合作的目的是改善药物的基因特征 人巨细胞病毒(CMV)的耐药性在艾滋病或其他疾病的受试者中 长期免疫抑制，巨细胞病毒病如视网膜炎倾向于 复发的情况，尽管维持抗病毒药物，最终仍会进展 心理治疗。目前尚不清楚疾病进展有多频繁是由于 宿主或药代动力学因素以及由CMV突变引起的频率 会导致抗药性。首席调查员和合作者， 与来自各自地理位置的抗药性分离株合作， 已经确定了UL97磷酸转移酶和DNA的许多突变 目前已知与药物有关的CMV聚合酶(POL)基因 抵抗。导致更昔洛韦耐药的UL97突变现在 定义相当明确，但POL中的抗药性突变具有 导致多重耐药的可能性还没有得到很好的研究。这个 接受治疗的受试者中耐药突变的演变，以及 不同身体部位病毒载量和表型的相关变化，需要 以便更好地界定，以指导临床实践。建议的贡献 一系列的样本、分离株和诊断技术 意大利的转诊实验室应该会更早地回答以下几个问题 重要的遗留问题。此次合作的具体目标是： 1.监测免疫低下的巨细胞病毒病患者的临床和 预测耐药性的病毒学变量，并选择样本用于 详细分析病毒耐药标志物。2.开发改进版 适用于临床的耐药表型快速检测方法 监测一个疗程的抗病毒治疗。3.基因特征 来自接受抗病毒治疗的患者的CMV分离株的变异性 在不同身体部位内和之间的病毒种群中， 导致耐药性的突变的存在，以及生物学上的 变异病毒的特性。