FACS ANALYSIS OF ANTIVIRAL DRUGS ON HCMV REPLICATION

描述(改编自申请人的摘要)：该项目的长期目标 项目是1)验证一种用于流式细胞仪的药物敏感性分析 具有对人类巨细胞病毒有效的抗病毒化合物；以及2) 论证了使用荧光标记的单抗的可行性 病毒抗原抗体和流式细胞术开始确定模式 这些抗病毒化合物的作用。人巨细胞病毒(HCMV)感染 是免疫功能低下患者发病率和死亡率的主要原因。 目前有三种获得许可的抗病毒药物可用于治疗巨细胞病毒。 该患者人群中的相关视网膜炎和一些新的抗病毒药物 化合物正在开发中。现行的药物检测程序 人巨细胞病毒临床分离株的敏感性耗时、劳动强度大、 和主观性。行动研究的模式也是劳动密集型和时间密集型的 在消费。需要更好的方法来测量磁化率 人巨细胞病毒化学分离株对抗病毒药物的耐药性及其作用模式(S)。小说 有效对抗人类巨细胞病毒感染的抗病毒药物是从 制药公司。药物敏感性和药物敏感性 对这些抗病毒药物耐药的巨细胞病毒实验室株和临床分离株 药物将使用这种流式细胞仪药敏试验进行评估。 即刻早期(IE)、早期和早期的荧光标记单抗 晚期HCMV抗原、DNA碘化丙啶染色和流式细胞术也 将用来开始阐释这些小说的动作模式(S 抗病毒化合物。介绍流式细胞仪技术在临床中的应用 抗病毒药物研究将加快发现更有效和更安全的药物 有效对抗巨细胞病毒的药物。这项流式细胞术技术的扩展 有效抗病毒药物的药物敏感性和作用模式研究 对其他病毒的攻击最终将使这种技术在 抗病毒研究。

DESCRIPTION (Adapted from applicant's abstract): The long term goals of this project are 1) to validate a flow cytometry drug susceptibility assay for use with antiviral compounds effective against human cytomegalovirus; and 2) to demonstrate the feasibility of using fluoroochrome labeled monoclonal antibodies to viral antigens and flow cytometry to begin to determine the mode of action of these antiviral compounds. Human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality in immunocompromised patients. There are three licensed antiviral drugs for use for treatment of HCMV associated retinitis in this patient population and a number of novel antiviral compounds are under development. The current procedures for determining drug susceptibility of HCMV clinical isolates are time consuming, labor intensive, and subjective. Mode of action studies are also labor intensive and time consuming. There is a need for better methods for measuring the susceptibility of HCMV chemical isolates to antiviral drugs and their mode(s) of action. Novel antiviral drugs effective against HCMV infection have been obtained from pharmaceutical companies. The susceptibilities of drug sensitive and drug resistant HCMV laboratory strains and clinical isolates to these antiviral drugs will be assessed using this flow cytometry drug susceptibility assay. Fluorochrome labeled monoclonal antibodies to immediate early (IE), early and late HCMV antigens, the DNA stain propidium iodide , and flow cytometry also will be used to begin to elucidate the mode(s) of action of these novel antiviral compounds. The introduction of flow cytometry technology for use in antiviral drug research will speed the discovery of more effective and safer drugs effective against HCMV. Extension of this flow cytometry technology for drug susceptibility and mode of action studies to antiviral drugs effective against other viruses will eventually make this a broadly used technique in antiviral research.