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; 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.

项目摘要/摘要 从2013年到2016年肆虐西非的埃博拉病毒流行是迄今为止记录的最大爆发。 较弱 流行病失控。然而，该地区对处理病毒出血的发烧并不陌生。 LASSA发烧是由Lassa病毒感染引起的，在西非是多流行。拉萨发烧相似 在感染LASSA病毒的埃博拉病毒中会导致严重的出血热。两种LASSA感染 超过70％的住院患者可能导致病毒和埃博拉病毒死亡。 据估计，每年成千上万的人死于Lassa热。这些数字可能是 低估，由于受益国家的医疗基础设施非常薄弱，监视 几乎不存在，而且大多数患者从未在医院出现。尽管病例死亡率很高 但是，住院的埃博拉病毒和LASSA发烧患者 病毒，而其他人则因感染而迅速死亡。然而，是什么与非致命疾病和非致命疾病区分开 症状与不对称感染的发展，在很大程度上尚不清楚并且严重 研究了。病毒系统生物学财团的目的是发现病毒和人为因素 这决定了感染者如何能够更好地结合病毒。我们将通过 调查以下三个广泛的目标： 目标1。定义病毒和宿主因素负责埃博拉病毒和非生存性的埃博拉病毒和非生存因素 患者。 目标2。确定因素在生存中的严重长期症状发展中起着作用的因素。 目标3。确定人类是有症状还是无症状的定义因素 疾病。 我们将通过应用几种“ OMIC”技术，物理测量以及 对LASSA热和埃博拉病毒的独特患者和生存队列的高通量实验方法。 我们将开发新的预测统计模型，以识别关键疾病相关并分析 大规模数据集以查明因果宿主 - 病原体相互作用。通过阐明分子网络 这种研究在患者的结果中起着至关重要的作用，这项研究将使我们能够确定药物的新目标和 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。