Consortium for Viral Systems Biology (CViSB)

修改后的项目摘要/摘要部分 2013年至2016年肆虐西非的埃博拉疫情是迄今为止规模最大的疫情 从未被记录过。薄弱的医疗基础设施、社区的抵抗以及缓慢而不协调的反应使疫情失控。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。拉沙热与埃博拉病毒的相似之处在于，感染拉沙病毒会导致严重的出血热。同时感染拉萨病毒和埃博拉病毒可能导致70%以上的住院患者死亡。 据估计，每年有数万人死于拉沙热。这些数字可能被低估了，因为受影响国家的医疗基础设施极其薄弱，几乎不存在监测，而且大多数患者从未出现在医院。然而，尽管住院的埃博拉和拉沙热患者的病死率很高，但一些人似乎能够迅速对抗病毒，而另一些人则很快死于感染。然而，致命性和非致命性疾病的区别以及症状性和无症状性感染的发展在很大程度上仍不清楚，研究严重不足。 最近的新冠肺炎全球大流行提出了与埃博拉和拉沙热相同的挑战和研究问题。病毒系统生物学联盟的目标是揭示病毒和人类因素，这些因素决定了受感染的人如何能够更好地对抗病毒。 我们将通过调查以下三个主要目标来实现这一目标： 目的1.明确导致埃博拉、拉沙热和新冠肺炎患者存活和死亡的病毒和宿主因素。 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.确定决定人类个体是否出现症状或 无症状的疾病。我们将通过将几种‘组学’技术、生理测量和高通量实验方法应用于独特的新冠肺炎、拉沙热和埃博拉病毒的患者和幸存者队列来实现这些目标。我们将开发新的预测统计模型来识别关键疾病相关性，并分析大规模数据集，以精确定位因果宿主-病原体相互作用。通过阐明在患者预后中发挥关键作用的分子网络，这项研究将使我们能够确定药物和疫苗的新靶点，并为个性化治疗策略提供信息。我们的研究还将提供新的研究框架和计算算法，适用于广泛的其他人类病原体。

Modified Project Summary/Abstract Section 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 recent COVID-19 global pandemic has presented identical challenges and research questions as Ebola and Lassa Fever. 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, Lassa fever and COVID-19 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 COVID-19, 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.