Consortium for Viral Systems Biology (CViSB)

项目摘要/摘要 2013年至2016年肆虐西非的埃博拉疫情是有记录以来最大规模的疫情。 薄弱的医疗基础设施，社区的抵制，以及缓慢而不协调的反应，使得 疫情失控。然而，该地区在应对病毒性出血热方面并不陌生。 拉沙热是由感染拉萨病毒引起的，在西非高度流行。拉沙热与此类似 由于感染拉萨病毒会导致严重的出血热，因此对埃博拉病毒的感染。两种拉萨病毒的感染 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。这些数字很可能是 低估了，由于受ff影响的国家的医疗基础设施极其薄弱，监测 几乎不存在，而且大多数患者从未出现在医院。尽管病死率很高， 然而，一些住院的埃博拉和拉沙热患者似乎能够迅速感染fi。 病毒，而其他人很快就会死于感染。然而，致命性和非致命性疾病和 有症状的感染与无症状的感染的发展在很大程度上仍不清楚，而且很严重 未得到充分研究。病毒系统生物学联盟的目标是发现病毒和人类因素 这决定了受感染的个体如何更好地fi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： 目的1.在埃博拉和拉沙热中，DefiNe病毒和宿主因素导致存活和死亡 病人。 目的2.确定在幸存者严重的长期症状发展过程中起作用的因素。 目标3.决定人类个体是否出现症状或无症状的Define因素 疾病。 我们将通过应用几种‘组学’技术、生理测量和 对独特的拉沙热和埃博拉患者和幸存者队列的高通量实验方法。 我们将开发新的预测统计模型，以识别危重疾病的相关性并进行分析 大规模数据集，以查明因果宿主与病原体的相互作用。通过阐明分子网络 对患者预后起关键作用，这项研究将使我们能够确定新的药物和 疫苗和告知个性化治疗策略。我们的研究还将提供新的研究框架 以及适用于广泛的其他人类病原体的计算算法。

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.