Understanding the Risk of Bat Coronavirus Emergence

了解蝙蝠冠状病毒出现的风险

• 批准号: 9491676
• 负责人: Peter Daszak
• 金额: $ 58.16万
• 依托单位: ECOHEALTH ALLIANCE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9491676
• 关键词: Affect; Animals; Asia; Binding; Binding Sites; Biological Assay; Blood specimen; Cell Culture Techniques; Cell Line; Cells; Chimeric Proteins; China; Chiroptera; Clinical; Coronavirus; Data; Dipeptidyl-Peptidase IV; Disease; Ecosystem; Epidemic; Evolution; Exposure to; Frequencies; Future; Genbank; Gene Proteins; Genes; Genetic; Genetic Recombination; Genetic Variation; Genomics; Geography; Human; In Vitro; Infection; Interview; Investigation; Laboratory Study; Mammals; Mathematics; Middle East; Middle East Respiratory Syndrome Coronavirus; Modeling; Molecular; Nature; Occupational Exposure; Pattern; Phylogenetic Analysis; Phylogeny; Primates; Process; Property; Public Health; Risk; Rural; SARS coronavirus; Sampling; Serological; Severe Acute Respiratory Syndrome; Site; Southeastern Asia; System; Testing; Viral; Viral reservoir; Virus; Virus Diseases; Work; Zoonoses; biosecurity; coronavirus receptor; experimental study; field study; global health; high risk; human population study; humanized mouse; improved; in vivo; interest; mathematical model; mutant; novel; pandemic disease; predictive modeling; public health relevance; receptor; receptor binding; reverse genetics; screening; trait; transmission process

DESCRIPTION (provided by applicant): This project will examine the risk of future coronavirus (CoV) emergence from wildlife using in-depth field investigations across the human-wildlife interface in China, molecular characterization of novel CoVs and host receptor binding domain genes, mathematical models of transmission and evolution, and in vitro and in vivo laboratory studies of host range. Zoonotic CoVs are a significant threat to global health, as demonstrated with the emergence of pandemic severe acute respiratory syndrome coronavirus (SARS-CoV) in China in 2002, and the recent and ongoing emergence of Middle East Respiratory Syndrome (MERS-CoV). Bats appear to be the natural reservoir of these viruses, and hundreds of novel bat-CoVs have been discovered in the last two decades. Bats, and other wildlife species, are hunted, traded, butchered and consumed across Asia, creating a large scale human-wildlife interface, and high risk of future emergence of novel CoVs. This project aims to understand what factors increase the risk of the next CoV emerging in people by studying CoV diversity in a critical zoonotic reservoir (bats), at sites of high risk for emergence (wildlife markets) in an emerging disease hotspot (China). The three specific aims of this project are to: 1. Assess CoV spillover potential at high risk human-wildlife interfaces in China. This will include quantifying he nature and frequency of contact people have with bats and other wildlife; serological and molecular screening of people working in wet markets and highly exposed to wildlife; screening wild-caught and market sampled bats from 30+ species for CoVs using molecular assays; and genomic characterization and isolation of novel CoVs. 2. Develop predictive models of bat CoV emergence risk and host range. A combined modeling approach will include phylogenetic analyses of host receptors and novel CoV genes (including functional receptor binding domains); a fused ecological and evolutionary model to predict host-range and viral sharing; and mathematical matrix models to examine evolutionary and transmission dynamics. 3. Test predictions of CoV inter-species transmission. Predictive models of host range (i.e. emergence potential) will be tested experimentally using reverse genetics, pseudovirus and receptor binding assays, and virus infection experiments across a range of cell cultures from different species and humanized mice.

描述（由申请人提供）：该项目将利用中国人类野生动物界面的深入现场调查，新颖的COV和宿主受体结合结构域的分子表征，传播和进化模型，传输和内膜实验室研究的数学模型以及主机研究的数学模型以及主机研究的数学模型。人畜共患病COV是对全球健康的重大威胁，这是2002年中国大流行严重的急性呼吸综合症冠状病毒（SARS-COV）的出现，以及中东呼吸道综合征（MERS-COV）的近期出现。蝙蝠似乎是这些病毒的天然储层，在过去的二十年中，已经发现了数百种新型的蝙蝠蛋白。蝙蝠和其他野生动植物物种在亚洲各地被猎捕，交易，屠宰和消费，创造了大规模的人野生生物界面，以及新型COV未来出现的高风险。该项目旨在了解哪些因素通过研究重要的人畜共患病（蝙蝠）中的COV多样性，在出现高风险（野生动植物市场）中，通过研究新兴疾病热点（中国）的高风险（野生动植物市场）来增加下一个COV的风险。该项目的三个具体目标是：1。评估中国人类野生动植物界面处于高风险的COV溢出潜力。这将包括量化人们与蝙蝠和其他野生动植物的联系的性质和频率；在湿市场工作的人们的血清学和分子筛查，并高度暴露于野生动植物；使用分子测定法对30多种COV的野生捕获和市场采样；以及新型COV的基因组表征和隔离。 2。开发BAT COV出现风险和宿主范围的预测模型。合并的建模方法将包括对宿主受体和新型COV基因（包括功能受体结合结构域）的系统发育分析；一种融合的生态和进化模型，以预测宿主范围和病毒分享；以及数学矩阵模型，以检查进化和传播动力学。 3。COV种间传输的测试预测。将使用反向遗传学，伪病毒和受体结合测定法以及跨不同物种和人文化小鼠的细胞培养物进行的病毒感染实验对宿主范围的预测模型（即出现电位）进行实验测试。