RAPID: Comparative genomics of SARS-CoV-2 susceptibility and immune defense in mammals

该项目的目标是比较数百种哺乳动物的基因组，发现DNA的差异，以区分对SARS-CoV-2具有抵抗力的物种和非常敏感的物种。需要这些信息来了解目前的SARS-CoV-2病毒如何传播给人类，并确定潜在的宿主动物（例如，宠物，牲畜和害虫物种）可能对SARS-CoV-2易感。引起COVID-19大流行的SARS-CoV-2可感染多种动物。不同物种之间对疾病的易感性和严重程度存在差异。这种变异表明，一些物种具有决定对COVID-19易感性的遗传差异。这项工作将确定冠状病毒如何适应新的宿主物种，这些信息将有助于预测和控制未来的冠状病毒爆发。资金将用于培训研究生，从而培训下一代生物经济劳动力。 该项目将研究宿主基因组如何塑造宿主-病原体相互作用，以及SARS-CoV-2等冠状病毒如何进化以利用新宿主。研究人员将使用三种互补方法比较数百种哺乳动物的现有基因组数据：（1）测量人类感染所必需的两种宿主蛋白ACE 2和TMPRSS 2的结构和序列同源性;（2）分析现有的RNA-seq数据集，以（a）鉴定在相同组织中共表达ACE 2和TMPRSS 2以及可能涉及感染的其他蛋白酶的物种，和（B）从不同哺乳动物物种中寻找偶然的冠状病毒序列数据;（3）使用正向基因组学测试与物种易感性相关的进化保守元件中的变体。通过这些分析，研究人员将确定有可能作为SARS-CoV-2病毒溢回人类的宿主的物种，以及那些有希望用于研究SARS-CoV-2进化，宿主防御和宿主-病原体相互作用的系统。 该RAPID奖项由BIO综合有机系统部门的生理和结构系统集群颁发，使用冠状病毒援助，救济和经济安全（CARES）法案的资金。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The goal of this project is to compare genomes of hundreds of mammal species, finding differences in DNA that distinguish species resistant to SARS-CoV-2 from those that are very susceptible. This information is needed to understand how the current SARS-CoV-2 virus spread to humans and to identify potential host animals (e.g., pet, livestock, and pest species) that may be susceptible to SARS-CoV-2 in the USA. SARS-CoV-2, the cause of the COVID-19 pandemic, can infect diverse species of animals. There is a variation in susceptibility to and severity of disease between species. This variation suggests that some species have genetic differences that dictate susceptibility to COVID-19. This work will identify how coronaviruses adapt to new host species, information that will help predict and control future coronavirus outbreaks. Funding will support training a graduate student in research, thereby training the next generation of the bioeconomy workforce. This project will investigate how the host genome shapes host-pathogen interactions, and how coronaviruses like SARS-CoV-2 evolve to exploit new hosts. The researchers will compare existing genomic data for hundreds of mammals using three complementary approaches: (1) Measure structural and sequence homology in two host proteins, ACE2 and TMPRSS2, necessary for infection in humans; (2) Analyze existing RNA-seq datasets to (a) identify species with co-expression of ACE2 and TMPRSS2, and potentially other proteases implicated in infection, in the same tissue, and (b) search for incidental coronaviral sequence data from diverse mammalian species; (3) Test for variants in evolutionarily conserved elements that are correlated with species susceptibility, using forward genomics. With these analyses, the researchers will identify species with potential as reservoirs for SARS-CoV-2 viral spillback into humans, and those that are promising systems for investigating SARS-CoV-2 evolution, host defenses, and host-pathogen interactions. This RAPID award is made by the Physiological and Structural Systems Cluster in the BIO Division of Integrative Organismal Systems, using funds from the Coronavirus Aid, Relief, and Economic Security (CARES) Act.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.