Viral Genomics: evolution, spread, and host interactions

病毒基因组学：进化、传播和宿主相互作用

• 批准号: 8959236
• 负责人: Bruce W. BIRREN
• 金额: $ 17.69万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-11-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8959236
• 关键词: Africa; American; Animal Model; Birds; Categories; Central America; Clinical; Collaborations; Communicable Diseases; Culicidae; Dengue Virus; Diagnosis; Diagnostic; Disease; Disease Outbreaks; Disease Progression; Endemic Diseases; Environment; Epidemic; Evolution; Fever; Fever of Unknown Origin; Genetic; Genome; Genomics; Genotype; Geographic Locations; Health; Human; Immune system; Individual; Infection; Institutes; Intervention; Investigation; Lassa virus; Latin America; Life Cycle Stages; Measures; Metadata; Microbe; Monitor; Nigeria; North America; Outcome; Pathogenesis; Pathology; Patients; Pharmaceutical Preparations; Population; Prevalence; Process; Public Health; RNA Viruses; Research; Research Personnel; Resources; Risk; Rodent; Sampling; Severity of illness; Sierra Leone; Site; Small RNA; South America; Symptoms; Technology; United States; Viral; Virus; Virus Diseases; West Nile virus; Widespread Disease; adaptive immunity; clinical research site; design; enzootic; genome wide association study; human disease; insight; microbial; mortality; pathogen; pressure; programs; sample collection; therapeutic vaccine; transmission process; vector

Rapid advances in genomic technologies are providing infectious disease researchers an unprecedented capability to study, at a genetic level, the viruses that cause disease and their interactions with infected hosts. The Broad Institute has led many technical and analytical advances that have enabled the genomic revolution and is one of the largest genome centers in the world. Our microbial genomics group has developed research programs in numerous viruses and has already sequenced over 6,500 viral strains from around the world. By leveraging the capacity and resources we have built in viral sequencing, as well as our field efforts and collaborations over the last decade, we will investigate three of the world's most important emerging infectious pathogens: Lassa Virus (LASV) and Dengue Virus (DENV), both Category A agents, and West Nile Virus (WNV), a Category B agent. These pathogens are notable for the high mortality, widespread disease and public health importance (in the US and elsewhere) they represent. Understanding how these small RNA viruses rapidly adapt to and escape from host selection pressures, including adaptive immune responses, is key to the design of viral diagnostics, vaccines and therapeutic drugs. Through our own efforts and through collaborations with clinicians and researchers, we have access to many important clinical and field samples that enable us to study not only viral evolution and spread within different geographic locations (Africa, South America and North America), but also viral adaptation within infected individuals. Rich collections of sample-associated metadata allow us to correlate viral genotype with disease severity and clinical outcome. Use of robust animal models of infection that recapitulate human disease progression will generate important insights into the pathology of LASV, DENV and WNV. Given the enzootic life cycle of these viruses, we are also investigating viral evolution and transmission within their natural hosts, which Include rodents, birds and mosquitos. Finally, we will take advantage of our existing global sample collection sites to investigate samples from patients who present symptoms similar to those caused by our diseases of study, but whose diagnoses remain unknown (FUOs, Fevers of Unknown Origin). Through these efforts we expect to better understand viral emergence and adaptation on a geographic scale as well as through the viral life cycle, from natural reservoirs to human infections. Detailed examination of viral diversity from field and clinical samples will provide remarkable insight into the dynamics of evolution and adaptation that are required for these viruses to emerge from isolated outbreaks to endemic disease with increasing health burdens worldwide.

基因组技术的快速发展为传染病研究人员提供了前所未有的能力， 在基因水平上研究引起疾病的病毒及其与受感染宿主的相互作用。布罗德研究所 引领了许多技术和分析方面的进步，使基因组革命成为可能， 基因组中心。我们的微生物基因组学小组已经开发了许多病毒的研究项目 并且已经对来自世界各地的6,500多个病毒株进行了测序。 通过利用我们在病毒测序方面建立的能力和资源，以及我们的实地工作， 在过去十年的合作中，我们将调查世界上三种最重要的新兴传染病， 病原体：拉沙病毒（LASV）和登革热病毒（DENV），均为A类病原体，以及西尼罗河病毒（WNV），a B类特工。这些病原体以其高死亡率、广泛传播的疾病和公共卫生而闻名 （在美国和其他地方）。了解这些小RNA病毒如何快速适应 逃避宿主选择压力，包括适应性免疫反应，是病毒诊断设计的关键， 疫苗和治疗药物。 通过我们自己的努力以及与临床医生和研究人员的合作，我们获得了许多重要的 临床和现场样本，使我们不仅能够研究病毒的演变和传播在不同的地理 在非洲、南美洲和北美洲，病毒的适应性也很重要。丰富 样本相关元数据的收集使我们能够将病毒基因型与疾病严重程度和临床 结果。使用重现人类疾病进展的强大的感染动物模型将产生重要的 深入了解LASV、DENV和WNV的病理学。考虑到这些病毒的地方性生命周期，我们也 调查病毒在其自然宿主（包括啮齿动物、鸟类和蚊子）中的进化和传播。 最后，我们将利用我们现有的全球样本采集点，调查来自以下患者的样本： 目前的症状与我们研究的疾病引起的症状相似，但其诊断仍然未知（FUO， 不明原因的发烧）。 通过这些努力，我们期望更好地了解病毒在地理范围内的出现和适应， 通过病毒的生命周期，从自然宿主到人类感染。田间病毒多样性的详细检查 临床样本将提供对进化和适应动力学的显着洞察， 这些病毒可能从孤立的爆发发展为地方性疾病，在全世界造成越来越大的健康负担。