DRUG RESISTANCE IN HUMAN CYTOMEGALOVIRUS

人类巨细胞病毒的耐药性

• 批准号: 6078389
• 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 2001-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6078389
• 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（改编自研究者摘要）：本国际 合作旨在改善药物的遗传特征 人巨细胞病毒（CMV）的耐药性。 艾滋病或其他疾病受试者 长期的免疫抑制，CMV疾病如视网膜炎往往是一个 尽管维持抗病毒治疗，但最终进展的复发性疾病 疗法 目前尚不清楚疾病进展的频率是由于 宿主或药代动力学因素以及CMV突变的频率 导致抗药性的病毒 主要研究者和合作者， 与来自各自地理位置的耐药菌株一起工作， 已鉴定出UL 97磷酸转移酶和DNA中的许多突变 CMV的聚合酶（Pol）基因，其迄今已知参与药物代谢。 阻力 现在，赋予更昔洛韦耐药性的UL97突变 相当明确的，但耐药突变的Pol，其中有 潜在的多药耐药性，研究较少。 的 治疗受试者中耐药突变的演变，以及 不同身体部位的病毒载量和表型的相关变化，需要 以更好地指导临床实践。 拟议捐款 系列标本，分离株和诊断技术，从一个建立 在意大利的转诊实验室应导致对几个问题的早期答复 剩下的重要问题。 这一合作的具体目标是： 1. 监测免疫功能低下的CMV疾病患者的临床和 预测耐药性的病毒学变量， 病毒耐药标志物的详细分析。 2. 开发改进的 适合使用的耐药性快速表型测定方法 监测一个疗程的抗病毒治疗 3. 遗传特征 CMV分离物来自接受抗病毒治疗的患者， 在不同身体部位内和之间的病毒种群中， 产生耐药性的突变的存在，以及生物学上的 突变病毒的特性。