RAPID: Collaborative Research: Immunological adaptations in bats to moderate the effect of coronavirus infection

COVID-19 颠覆了社会的方方面面。虽然大多数研究都集中在临床应用上，但 SARS-CoV2 的祖先如何在自然界中生存和传播对于预防未来的流行病和帮助卫生专业人员开发治疗方法至关重要。由于一些蝙蝠物种是许多冠状病毒的天然携带者，包括已知的与 SARS-CoV-2 最近的亲属，因此该奖项支持的团队将确定蝙蝠和其他哺乳动物之间的一致差异，这些差异可能与通过调节病毒进入和建立有效的免疫反应来调节感染有关。该项目将解决蝙蝠如何在携带多种病毒的情况下逃避疾病。作为这项工作的一部分，研究团队将开发与蝙蝠免疫学相关的教育展示，以便在德克萨斯理工大学博物馆公开展示。该研究的结果也将发表在同行评审期刊上，在科学会议上发表，并发布到共享数据存储库。该奖项支持的研究人员假设，与其他哺乳动物相比，蝙蝠免疫反应途径中涉及的基因存在一致的差异，例如：a）蝙蝠表现出不成比例的独特基因组适应； b) 蝙蝠体内的免疫系统基因表达量高于同类小鼠和人类组织；c) 蝙蝠体内参与冠状病毒细胞进入的基因表达量在 RNA 谱上有所不同，与人类和小鼠相比，限制了发病机制的程度。为了检验这些假设，该团队将在病毒趋向性和免疫反应的背景下分析不同蝙蝠物种的基因组结构，并对不同组织进行差异表达分析。结果数据将为研究人员和临床医生预测和治疗这些呼吸系统综合症提供信息。该 RAPID 奖项由 BIO 综合有机系统部门的生理和结构系统集群使用冠状病毒援助、救济和经济安全 (CARES) 法案的资金颁发。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

All aspects of society have been upended by COVID-19. While most research has understandably focused on clinical applications, how the ancestors of SARS-CoV2 survive and circulate in nature is vital to both prevent future epidemics and help health professionals develop therapeutic treatments. Because some bat species are natural carriers of many coronaviruses, including the closest known relatives of SARS-CoV-2, the team supported by this award will identify consistent differences between bats and other mammals likely involved in moderating infection by regulating virus entry and mounting an effective immune response. This project will address how bats escape illness despite carrying a wide range of viruses. As part of this work, the research team will develop educational displays related to the bat immunology for public display at the Museum of Texas Tech. Results for the study will also be published in peer-reviewed journals, presented at scientific meetings, and posted to shared data repositories.Researchers supported by this award hypothesize there are consistent differences in the genes involved in the immune response pathways of bats compared to other mammals, such that: a) bats show disproportionate numbers of unique genomic adaptations; b) there is higher expression of immune system genes in bats than in comparable mouse and human tissues, and c) expression of genes involved in coronavirus cell entry in bats differs in RNA profile, limiting the extent pathogenesis when compared to humans and mice. To test these hypotheses, the team will analyze genome structure across diverse bats species, and differential expression analysis of different tissues, in the context of viral tropism and immune response. Resulting data will inform researchers and clinicians as they anticipate and treat these respiratory syndromes. 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.