Deciphering long-term virus evolution through the reconstruction of past viral genomes

通过重建过去的病毒基因组来破译病毒的长期进化

• 批准号: 10725830
• 负责人: Daniel Blanco-Melo
• 金额: $ 53.48万
• 依托单位: FRED HUTCHINSON CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10725830
• 关键词: 2019-nCoV; Address; Calibration; Cells; Collection; Complement; DNA; DNA Viruses; Development; Disease; Disease Outbreaks; Documentation; Ebola virus; Epidemic; Etiology; Evolution; Family; Forensic Medicine; Future; Genome; Genomics; Goals; Great Britain; HIV; Human; Immunology; Individual; Industrialization; Influenza A virus; Knowledge; Lead; Life Cycle Stages; Link; Measles; Medical; Methodology; Mexico; Modeling; Modernization; Molecular; Morbidity - disease rate; Museums; Paleontology; Pathogenesis; Pathogenicity; Pathology; Poliomyelitis; Population; Positioning Attribute; Prevention strategy; Property; Proteomics; Protocols documentation; RNA; RNA Viruses; Recording of previous events; Records; Research; Respiratory Tract Infections; Sampling; Smallpox; Spain; Specimen; Symptoms; Techniques; Variant; Viral; Viral Genes; Viral Genome; Viral Proteins; Virulent; Virus; Virus Diseases; Work; career; clinically significant; ds-DNA; human pathogen; improved; innovation; lung preservation; microbial genome; molecular clock; mortality; multidisciplinary; novel strategies; pandemic disease; pathogen; pathogenic virus; post-doctoral training; previous epidemic; protein function; reconstruction; skills; socioeconomics; symptomatology; synergism; technology development; tissue tropism; transmission process; viral RNA; viral epidemic; viral outbreak; viral pandemic; virology; virus identification

Project Summary Viruses have imposed a significant global burden of morbidity and mortality for millennia. Just in the last century, highly pathogenic RNA viruses such as influenza A, HIV and SARS-CoV-2 resulted in devastating pandemics that directly impacted millions of individuals and altered socioeconomic dynamics worldwide. Fueled by major advances in sequencing during the last decades, the emerging field of archeovirology has begun identifying viruses that severely impacted humans prior to the 20th century. To this day, however, the pathogens responsible for important past epidemics are still unknown and there are significant gaps remaining in the evolutionary history of certain viral families, especially for RNA viruses. Using a highly collaborative and innovative approach to overcome intrinsic limitations in the identification of viral genomes from human remains, this proposal will uncover the viral diversity that existed during periods of notable epidemic outbreaks and expand our knowledge of the origins and evolution of highly pathogenic viruses. In particular, this proposal seeks to identify and characterize genomes from centuries-old RNA viruses, a goal that so far has remained elusive. Using well-established ancient DNA techniques, forensic proteomics, and improved RNA isolation methodologies, our team will reconstruct viral genomes from human remains of deadly epidemics in early colonial Mexico and preserved lung specimens from pathology collections corresponding to the industrial revolution in Great Britain. Guided by archeological and historical documentation in these two distinct historical contexts, this work will identify viruses that existed in the past ~500 years, study their origin and evolutionary relationships to modern viruses, and characterize the evolution of viral protein function in relation to their human hosts. Together, this proposal will generate a comprehensive characterization of the properties of past viral infections that will not only lead to the identification of viruses responsible for epidemics that profoundly altered human history but will also uncover evolutionary adaptations between past and present viruses and define the origins of highly pathogenic RNA viruses, providing key molecular information to prepare against the (re)emergence of highly virulent viruses in the future.

项目摘要 数千年来，病毒给全球带来了巨大的发病率和死亡率负担。就在最近 世纪以来，高致病性RNA病毒如甲型流感、HIV和SARS-CoV-2导致了毁灭性的 这些流行病直接影响到数百万人，改变了全世界的社会经济动态。 在过去的几十年里，随着测序技术的重大进步，考古病毒学的新兴领域已经 开始鉴定在世纪之前严重影响人类的病毒。然而，时至今日， 导致过去重大流行病的病原体仍然未知， 在某些病毒家族的进化史上，尤其是RNA病毒。使用高度协作和 创新的方法，以克服固有的局限性，在确定病毒基因组从人类遗骸， 该提案将揭示在显著流行病爆发期间存在的病毒多样性， 扩大我们对高致病性病毒的起源和进化的了解。特别是，这项建议 试图从几个世纪前的RNA病毒中识别和描述基因组，这是一个迄今为止仍然存在的目标。 难以捉摸。使用成熟的古代DNA技术，法医蛋白质组学和改进的RNA分离 方法，我们的团队将重建病毒基因组从人类遗骸的致命流行病在早期 墨西哥殖民地和保存的肺标本从病理学收集对应的工业 英国的革命。在这两个不同历史时期的考古和历史文献的指导下， 在这种背景下，这项工作将确定在过去500年中存在的病毒，研究它们的起源和进化 与现代病毒的关系，并表征病毒蛋白质功能的演变与其 人类宿主总之，这一建议将产生一个全面的特性，过去的 病毒感染，这不仅将导致确定病毒负责的流行病， 改变了人类历史，但也将揭示过去和现在的病毒之间的进化适应， 确定高致病性RNA病毒的起源，提供关键的分子信息， 未来可能会出现高毒力病毒。