Flow-enhanced characterization of drug-resistant viruses

耐药病毒的流式增强表征

基本信息

批准号：
8136758
负责人：
John Yin
金额：
$ 1.8万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8136758
关键词：
Acquired Immunodeficiency Syndrome Address Applications Grants Area Basic Science Biological Biological Models Cell Culture Techniques Cell Death Cells Clinic Common Cold Disease Drug resistance Effectiveness Gene Expression Growth Health Hepatitis Human Human Virus Infection Influenza Laboratories Laboratory culture Light Malignant Neoplasms Measurement Measures Medical Methodology Methods Microfluidics Molecular Morphology Patients Pattern Pharmaceutical Preparations Plaque Assay Population Production Public Health Research Risk Severe Acute Respiratory Syndrome Therapeutic Time Vesicular stomatitis Indiana virus Viral Viral Genes Viral Hemorrhagic Fevers Virion Virus Virus Diseases base digital imaging disease diagnosis drug resistant virus effective therapy fluid flow novel strategies performance tests technology development

项目摘要

DESCRIPTION (provided by applicant): Viruses pose a significant threat to human health based on their ability to cause diseases such as acquired immunodeficiency syndrome (AIDS), influenza, hepatitis, cancer, severe acute respiratory syndrome (SARS), hemorrhagic fever and the common cold. Quantitative assessments of virus infectivity are important in the clinic to test the performance of anti-viral drugs on patient isolates as well as to assess the effectiveness of drug treatments over time. Measures of infectivity are also important in basic research to elucidate the molecular-level mechanisms of virus growth and develop effective anti-viral therapeutics or strategies. Established methods for the determination of virus infectivity, such as the plaque assay, lack sensitivity and are both time consuming and labor intensive to implement. The objective of this Technology Development for Biomedical Applications Grant (R21) is to develop a better way to measure the infectivity of viruses. The proposed method: (a) uses micro-scale fluid flows to control and enhance the growth and spread of viruses on host-cell cultures, and (b) employs digital imaging to characterize and quantify spatial patterns of infection. As a model system the flow-enhanced spread of vesicular stomatitis virus (VSV) will be studied because VSV can be readily cultured in the laboratory and is minimally pathogenic to humans. Preliminary results demonstrate for the first time that it is feasible to implement, detect, and enhance the spread of virus infections in a microfluidic channel. Specific aims of the proposed project will be to: (1) characterize how fluid flow influences virus production by infected cells, (2) elucidate the effects of fluid flow on the morphology of infection comets formed in micro-channels, and (3) employ comet-size distributions to characterize drug resistance in virus populations. The methodology established by this research will set a basis for advancing the characterization of viruses of human medical importance. Viruses cause diseases such as AIDS, influenza, and cancer, and thereby pose a significant risk to public health. Measurements of virus infectivity are important for diagnosing disease in patients and prescribing effective treatments, but current measurement methods lack sensitivity and are labor-intensive to perform. The proposed research aims to address these limitations by advancing a new approach that is both more sensitive and easy to perform.

描述（由申请人提供）：病毒对人类健康构成重大威胁，因为它们能够引起获得性免疫缺陷综合症（艾滋病）、流感、肝炎、癌症、严重急性呼吸系统综合症（SARS）、出血热和常见疾病等疾病。寒冷的。病毒感染性的定量评估对于临床测试抗病毒药物对患者分离株的性能以及评估药物治疗随时间的有效性非常重要。感染性的测量对于阐明病毒生长的分子水平机制并开发有效的抗病毒疗法或策略的基础研究也很重要。确定病毒感染性的既定方法（例如噬菌斑测定）缺乏敏感性，并且实施起来既耗时又费力。这项生物医学应用技术开发补助金 (R21) 的目标是开发一种更好的方法来测量病毒的感染性。所提出的方法：（a）使用微尺度流体流动来控制和增强病毒在宿主细胞培养物上的生长和传播，以及（b）采用数字成像来表征和量化感染的空间模式。作为模型系统，我们将研究水疱性口炎病毒（VSV）的流动增强传播，因为 VSV 可以在实验室中轻松培养，并且对人类的致病性极低。初步结果首次证明在微流体通道中实施、检测和增强病毒感染的传播是可行的。该项目的具体目标是：（1）表征流体流动如何影响受感染细胞的病毒产生，（2）阐明流体流动对微通道中形成的感染彗星形态的影响，以及（3）采用彗星大小的分布来表征病毒群体的耐药性。这项研究建立的方法将为推进具有人类医学重要性的病毒的表征奠定基础。病毒会引起艾滋病、流感和癌症等疾病，从而对公共健康构成重大风险。病毒感染性的测量对于诊断患者的疾病和制定有效的治疗方法很重要，但目前的测量方法缺乏敏感性，并且执行起来需要耗费大量人力。拟议的研究旨在通过提出一种更灵敏且易于执行的新方法来解决这些局限性。