Understanding the Risk of Bat Coronavirus Emergence

了解蝙蝠冠状病毒出现的风险

• 批准号: 8674931
• 负责人: Peter Daszak
• 金额: $ 66.64万
• 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/8674931
• 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; Genes; Genetic; Genetic Recombination; Genetic Variation; Genomics; Human; Human Virus; In Vitro; Infection; Interview; Investigation; Laboratory Study; Life; Mammals; Marketing; Middle East; Modeling; Molecular; Mus; 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; Syndrome; System; Testing; Viral; Virus; Virus Diseases; Work; biosecurity; coronavirus receptor; field study; global health; high risk; human population study; improved; in vitro Assay; in vivo; interest; mathematical model; mutant; novel; pandemic disease; positional cloning; predictive modeling; public health relevance; receptor; receptor binding; research study; respiratory; 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）：该项目将通过对中国人类与野生动物界面的深入实地调查、新型冠状病毒和宿主受体结合域基因的分子特征、数学传播和进化模型，以及宿主范围的体外和体内实验室研究。人畜共患冠状病毒对全球健康构成重大威胁，2002 年中国出现的大流行性严重急性呼吸综合征冠状病毒 (SARS-CoV) 以及最近持续出现的中东呼吸综合征 (MERS-CoV) 就证明了这一点。蝙蝠似乎是这些病毒的天然宿主，在过去二十年中已经发现了数百种新型蝙蝠冠状病毒。蝙蝠和其他野生动物物种在亚洲各地被猎杀、交易、屠宰和消费，造成了大规模的人类与野生动物接触，并且未来出现新型冠状病毒的风险很高。该项目旨在通过研究新兴疾病热点地区（中国）出现高风险地区（野生动物市场）的关键人畜共患宿主（蝙蝠）中的冠状病毒多样性，了解哪些因素会增加人类中出现下一次冠状病毒的风险。该项目的三个具体目标是： 1. 评估中国高风险人类与野生动物接触面的冠状病毒溢出潜力。这将包括量化人们与蝙蝠和其他野生动物接触的性质和频率；对在生鲜市场工作并高度接触野生动物的人员进行血清学和分子筛查；使用分子检测对来自 30 多个物种的野生捕获和市场采样的蝙蝠进行 CoV 筛查；以及新型冠状病毒的基因组表征和分离。 2. 开发蝙蝠冠状病毒出现风险和宿主范围的预测模型。组合建模方法将包括宿主受体和新型冠状病毒基因（包括功能性受体结合域）的系统发育分析；用于预测宿主范围和病毒共享的融合生态和进化模型；和数学矩阵模型来检查进化和传播动力学。 3.测试对冠状病毒种间传播的预测。宿主范围（即出现潜力）的预测模型将使用反向遗传学、假病毒和受体结合测定以及来自不同物种和人源化小鼠的一系列细胞培养物的病毒感染实验进行实验测试。