Collaborative Research: PurSUiT: Systematic viral discovery through structured search of host phylogeny

病毒病原体通常在出现并在人类或家畜中引起疾病后进行深入研究。这导致了对少数影响人类的病毒的深刻理解，但在很大程度上忽略了其余哺乳动物中巨大的、未知的病毒多样性。该项目利用自然历史博物馆中储存的高质量、低温冷冻的野生哺乳动物组织收藏品，系统地对哺乳动物生命树上的病毒多样性进行测序、发现和表征。该项目将直接有助于了解宿主病毒的进化，告知“溢出”或宿主转换发生的频率和距离，并识别高风险和低风险的病毒病原体。通过将病毒序列连接回博物馆的哺乳动物实物标本，该项目为未来对特定病原体、病原体群落及其哺乳动物宿主中相关的遗传变异进行详细研究奠定了基础。为了进一步加强微生物研究和自然历史博物馆之间的联系，该项目将与ECHO项目的博物馆和美洲新兴病原体(MEPA)网络合作，促进国际思想交流，并在更有可能出现病原体的生物多样性国家建设能力。该项目使用一种优化进化距离和地理覆盖面的抽样策略来选择哺乳动物样本来调查病毒。最初，27个目中的25个目近600个哺乳动物物种的核心集合将成为目标，以提供全哺乳动物范围的病毒多样性调查。基于这一初步努力，将选择拥有特别丰富的病毒群落的谱系进行更密集的采样，以便分析病毒与病毒的相互作用和宿主病毒的共同进化(或缺乏这种分析)。新的和已知的病毒序列将被生物信息重建，并用于测试与病毒多样性、宿主特征和宿主多样性有关的长期假设，包括哪些谱系代表对人类的“高风险”或“低风险”(例如，蝙蝠、啮齿动物和灵长类动物作为传统的“高风险”群体)。宿主转换率升高的哺乳动物和病毒谱系对将被用来识别与此类事件相关的生态和环境特征。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Viral pathogens are usually researched intensively after they emerge and cause disease in humans or domestic animals. This leads to a deep understanding of the few viruses that affect humans, but largely ignores the vast, unknown diversity of viruses in the rest of mammals. This project leverages the high-quality, cryogenically frozen tissue collections of wild mammals that are stored in natural history museums to systematically sequence, discover, and characterize viral diversity from across the Mammal Tree of Life. This project will contribute directly to the understanding of host-virus evolution, inform the frequency and distance at which ‘spillover’ or host-switches can occur, and identify high and low risk viral pathogens. By connecting the viral sequences back to a physical mammal specimen at a museum, this project provides a foundation for detailed future investigations of specific pathogens, pathogen communities, and the associated genetic variation in their mammal hosts. To further reinforce the connection between microbial research and natural history museums, this project will collaborate with Project ECHO’s Museums and Emerging Pathogens in the Americas (MEPA) network to foster international exchange of ideas and build capacity in biodiverse countries, where pathogen emergence is more likely. This project uses a sampling strategy that optimizes evolutionary distances and geographic coverage to select mammal specimens to survey for viruses. Initially, a core set of nearly 600 mammalian species in 25 of 27 orders will be targeted to provide a mammal-wide survey of viral diversity. Based on this initial effort, lineages that have especially rich viral communities will be selected for more intensive sampling that will allow for analyses of virus-virus interactions and host-virus co-evolution (or lack thereof). New and known viral sequences will be reconstructed bioinformatically and used to test long-standing assumptions related to viral diversity, host traits, and host diversity, including which lineages represent “high risk” or “low risk” to humans (e.g., bats, rodents, and primates as traditionally “high risk” groups). Pairs of mammal and virus lineages that show elevated rates of host switching will be used to identify the ecological and environmental traits that are associated with such events.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.