Epidemiology and Pathogenesis of Novel Coronaviruses

新型冠状病毒的流行病学和发病机制

• 批准号: 7817064
• 负责人: SAMUEL Richard DOMINGUEZ
• 金额: $ 13.23万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7817064
• 关键词: Acute; Age; Animals; Antibodies; Asia; Base Sequence; Binding; Biological Assay; Birds; Cells; Childhood; Chiroptera; Clinical; Clinical Virology; Collaborations; Collection; Communicable Diseases; Coronavirus; Coronavirus spike protein; Data; Diagnostic; Disease; Disease Association; Ecology; Emerging Communicable Diseases; Enteral; Epidemic; Epidemiology; Feces; Genes; Genetic Variation; Glycoproteins; Goals; Human; Infection; Laboratories; Mediating; Mentors; Molecular; Nucleocapsid; Pathogenesis; Patients; Pediatric Hospitals; Phylogenetic Analysis; Prevalence; Proteins; RNA; RNA Viruses; Reagent; Recombinants; Research; Research Personnel; Research Training; Resources; Retroviridae; Reverse Transcriptase Polymerase Chain Reaction; Role; Salivary; Sampling; Screening procedure; Seroprevalences; Severe Acute Respiratory Syndrome; Specialist; Specimen; Tissues; Training; Virus; cDNA Library; coronavirus receptor; economic impact; experience; human coronavirus; infancy; insight; novel; pandemic disease; progenitor; programs; rapid diagnosis; receptor; replicase; respiratory; tool

DESCRIPTION (provided by applicant): Severe acute respiratory syndrome (SARS), caused by a new human coronavirus (SARS-CoV), represents the 21st century's first pandemic caused by a previously unknown etiological agent. The 2002-03 SARS epidemic stimulated research on coronaviruses of humans, animals, and birds. SARS had enormous economic impact and demonstrated the pathogenic potential of this large group of RNA viruses. An indirect result of the SARS epidemic was the discovery of two new human coronaviruses, HCoV-NL63, isolated in 2004, and HCoV-HKU1, discovered in 2005, and the discovery of novel bat coronaviruses in Asia. Interestingly, preliminary phylogenetic analysis suggests that all animal and human coronaviruses may have evolved from progenitor coronaviruses in bats. Studies on the epidemiology and pathogenesis of NL63, HKU1, and bat coronaviruses are still in their infancy. My mentor's laboratory has extensive experience in studying human and animal coronaviruses. Because I am a pediatric infectious disease specialist with a collaboration already established with The Children's Hospital Clinical Virology Laboratory, an outstanding collection of pediatric respiratory and stool specimens is available to me. Additionally, my mentor and I have joined the recently formed Rocky Mountain Bat Research Consortium. These combined advantages provide me with the needed resources and training for this proposed research. In this revised K08 application, I propose epidemiological, functional and molecular characterization studies on NL63, HKU1, and novel Rocky Mountain bat coronaviruses (RM-BtCoV), which I recently discovered. My goals are to develop sensitive and specific new tools for the rapid diagnosis of these viruses; characterize their prevalence, diversity and clinical spectra; and identify candidate receptor(s) for RM-BtCoVs. These studies will generate needed and valuable reagents for further studies on these viruses, provide information regarding the roles of NL63 and HKU1 in pediatric diseases, and provide further insights into the evolutionary relationships of coronaviruses and mechanisms of emergence of zoonotic diseases. The training and research on emerging coronaviruses that I propose here will enable me to study the essential components of emerging infectious diseases caused by other viruses, including their epidemiology, ecology, diagnostics, disease associations, and zoonotic emergence.

描述（由申请人提供）：由新的人类冠状病毒（SARS-COV）引起的严重急性呼吸综合征（SARS），代表了21世纪由以前未知的病因学剂引起的第21世纪大流行。 2002-03 SARS流行刺激了对人，动物和鸟类的冠状病毒的研究。 SARS具有巨大的经济影响，并证明了这种大量RNA病毒的致病潜力。 SARS流行的间接结果是发现了两种新的人类冠状病毒，HCOV-NL63，于2004年分离出来，在2005年发现了HCOV-HKU1，并发现了亚洲的新型BAT冠状病毒。有趣的是，初步的系统发育分析表明，所有动物和人类冠状病毒可能都是从蝙蝠中的祖细胞冠状病毒演变而来的。 NL63，HKU1和BAT冠状病毒的流行病学和发病机理的研究仍处于起步阶段。我的导师的实验室在研究人类和动物冠状病毒方面具有丰富的经验。由于我是一名儿童传染病专家，并与儿童医院临床病毒学实验室建立了合作，因此我可以使用出色的小儿呼吸和粪便标本。此外，我和我的导师加入了最近成立的落基山蝙蝠研究联盟。这些合并的优势为我提供了这项拟议研究所需的资源和培训。在此修订后的K08应用中，我提出了我最近发现的NL63，HKU1和新型落基山蝙蝠冠状病毒（RM-BTCOV）的流行病学，功能和分子表征研究。我的目标是为快速诊断这些病毒开发敏感和特定的新工具。表征它们的流行，多样性和临床光谱；并确定RM-BTCOV的候选受体。这些研究将产生有关这些病毒的进一步研究所需和有价值的试剂，提供有关NL63和HKU1在小儿疾病中的作用的信息，并提供对冠状病毒的进化关系以及生物性疾病出现机制的进一步见解。我在这里提出的有关新兴冠状病毒的培训和研究将使我能够研究由其他病毒引起的新兴传染病的基本组成部分，包括其流行病学，生态学，诊断，疾病关联和人畜共患病。