Consortium for Viral Systems Biology (CViSB)

病毒系统生物学联盟 (CViSB)

• 批准号: 10248803
• 负责人: Kristian Graugaard Andersen
• 金额: $ 25万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10248803
• 关键词: Address; Affect; Africa; Binding; Biological; Case Fatality Rates; Cessation of life; Clinical; Communities; Computational algorithm; Country; Data Set; Development; Disease; Disease Marker; Disease Outbreaks; Ebola; Ebola Hemorrhagic Fever; Ebola virus; Epidemic; Future; Genetic; Goals; Healthcare; Hospitals; Human; Immunologics; Immunotherapeutic agent; Individual; Infection; Infrastructure; Integration Host Factors; Investigation; Lassa Fever; Lassa virus; Lead; Measurement; Medicine; Mission; Molecular; Outcome; Outcomes Research; Patient-Focused Outcomes; Patients; Physiological; Play; Research; Research Infrastructure; Resistance; Role; Severities; Statistical Models; Survivors; Symptoms; System; Systems Biology; Technology; Vaccines; Viral; Viral Hemorrhagic Fevers; Virus; Work; cohort; data access; data tools; fighting; human disease; human pathogen; innovation; insight; large scale data; member; microbial; neutralizing antibody; novel; pathogen; personalized medicine; predictive marker; predictive modeling; programs; response; treatment strategy

Project Summary/Abstract The Ebola epidemic that ravaged West Africa from 2013 to 2016 is by far the largest outbreak ever recorded. Weak healthcare infrastructure, community resistance, and a slow uncoordinated response, allowed the epidemic to spin out of control. The region, however, is no stranger to dealing with viral hemorrhagic fevers. Lassa fever is caused by infection with Lassa virus and is hyper-endemic in West Africa. Lassa fever is similar to Ebola in that infection with Lassa virus can lead to a severe hemorrhagic fever. Infections with both Lassa virus and Ebola virus can lead to deaths in more than 70% of hospitalized patients. It is estimated that tens of thousands of people die from Lassa fever each year. These numbers are likely underestimates, as the healthcare infrastructure in the affected countries is extremely weak, surveillance almost non-existent, and most patients never present in the hospital. Despite the high case fatality rates of hospitalized Ebola and Lassa fever patients, however, some people appear to be able to quickly fight the viruses, whereas others die quickly from infection. Yet, what distinguishes fatal from non-fatal disease and the development of symptomatic versus asymptomatic infection, remain largely unknown and severely understudied. The goal of the Consortium for Viral Systems Biology is to uncover the virus and human factors that determine how infected individuals are able to better fight the viruses. We will achieve this goal by investigating the following three broad aims: Aim 1. Define virus and host factors responsible for survival and non-survival in Ebola and Lassa fever patients. Aim 2. Identify factors that play roles in the development of severe long-term symptoms in survivors. Aim 3. Define factors that determine whether human individuals develop symptomatic or asymptomatic disease. We will accomplish these aims by applying several ‘omics’ technologies, physiological measurements, and high-throughput experimental approaches to unique patient and survivor cohorts of Lassa fever and Ebola. We will develop novel predictive statistical models for identifying critical disease correlates and analyze large-scale data sets to pinpoint causal host-pathogen interactions. By elucidation the molecular networks that play critical roles in patient outcomes, this research will allow us to identify new targets for medicines and vaccines and inform personalized treatment strategies. Our study will also provide novel research frameworks and computational algorithms applicable to a wide range of other human pathogens.

项目概要/摘要 2013年至2016年肆虐西非的埃博拉疫情是迄今为止有记录以来最大规模的疫情。 薄弱的医疗基础设施、社区抵制以及缓慢且不协调的反应，使得 疫情失控。然而，该地区对病毒性出血热并不陌生。 拉沙热是由拉沙病毒感染引起的，在西非高度流行。拉沙热有相似之处 埃博拉病毒感染拉沙病毒可导致严重的出血热。两种拉沙病毒感染 病毒和埃博拉病毒可导致70%以上的住院患者死亡。 据估计，每年有数万人死于拉沙热。这些数字很可能 低估了，由于受影响国家的医疗基础设施极其薄弱，监测 几乎不存在，大多数患者从未到过医院。尽管病死率很高 然而，在住院的埃博拉和拉沙热患者中，有些人似乎能够迅速对抗病毒 病毒，而其他病毒则因感染而很快死亡。然而，致命疾病与非致命疾病的区别是什么？ 有症状感染与无症状感染的发展仍然很大程度上未知且严重 待研究。病毒系统生物学联盟的目标是揭示病毒和人为因素 决定感染者如何更好地对抗病毒。我们将通过以下方式实现这一目标 调查以下三个主要目标： 目标 1. 确定导致埃博拉和拉沙热存活和不存活的病毒和宿主因素 患者。 目标 2. 确定在幸存者出现严重长期症状的过程中发挥作用的因素。 目标 3. 定义决定人类个体是否出现有症状或无症状的因素 疾病。 我们将通过应用多种“组学”技术、生理测量和 针对拉沙热和埃博拉病毒的独特患者和幸存者群体的高通量实验方法。 我们将开发新的预测统计模型来识别危重疾病的相关性并进行分析 大规模数据集可查明宿主与病原体之间的因果相互作用。通过阐明分子网络 在患者治疗结果中发挥关键作用，这项研究将使我们能够确定药物和药物的新目标 疫苗并为个性化治疗策略提供信息。我们的研究还将提供新颖的研究框架 以及适用于多种其他人类病原体的计算算法。