US-UK Collab: Modelling reassortment at the cellular, clinical, and phylogenetic level in emerging Bunyaviruses

美英合作：在新兴布尼亚病毒的细胞、临床和系统发育水平上模拟重配

• 批准号: 10379508
• 负责人: Carmen Molina-Paris
• 金额: $ 45.57万
• 依托单位: TRIAD NATIONAL SECURITY, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10379508
• 关键词: Address; Affect; Arthropods; Bunyaviridae; Cells; Clinical; Crimean Hemorrhagic Fever; Crimean-Congo Hemorrhagic Fever Virus; Data; Data Collection; Data Set; Disease; Disease Outbreaks; Ecology; Ensure; Epidemic; Epidemiology; Evolution; Family; Frequencies; Gene Expression; Genes; Genetic Enhancement; Genetic Recombination; Genome; Genotype; Health; Human; In Vitro; Infection; Influenza A virus; Joints; Life Cycle Stages; Meleagris gallopavo; Mentors; Methods; Modeling; Orthobunyavirus; Other Genetics; Phylogenetic Analysis; Phylogeny; Play; Point Mutation; Population; Postdoctoral Fellow; Prevention approach; Process; Protocols documentation; Public Health; RNA; Recording of previous events; Research; Research Personnel; Risk; Role; Sampling; Standardization; Tajikistan; Ticks; Time; Vertebrates; Viral Genes; Virion; Virus; Virus Replication; Work; biobank; improved; laboratory experiment; mathematical model; novel; novel virus; pandemic disease; public health emergency; research and development; transmission process; vector; viral transmission

Genome segmentation has important implications for viral gene expression control and RNA assembly into nascent virions. It also creates the potential for reassortment: the exchange of intact gene segments between viruses that coinfect the same cell. Reassortment is different from recombination since it allows many distinct genotypes to emerge from a single coinfected cell. Not only does segmentation enhance genetic diversification but it plays a unique role in the evolutionary history of segmented viruses due to the rare occasions when a reassortant is successful at a population scale. A striking example from the Bunyaviridae family of the emergence of a novel virus through reassortment is that of Ngari virus. For influenza A (IAV), the best characterised segmented virus, reassortment has facilitated the formation of pandemic strains in 1957, 1968 and 2009. Out of seven epidemic-prone diseases prioritized by the WHO 2018 R&D Blueprint as public health emergencies with an urgent need for accelerated research, three are Bunyaviruses: Lassa, Rift Valley and Crimean-Congo hemorrhagic fevers. Thus, the overarching hypothesis of this project is that reassortment of segmented viruses plays a major role not only to drive their diversification and evolution, but to dramatically alter their ecology and transmission dynamics. Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses to quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised sequencing protocols and novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV). A biobank with clinical and field samples from CCHFV endemic regions in Turkey and Tajikistan will be set up in this project. Clinical and field data will be leveraged to ensure our methods and results have the potential to inform public health strategies, predict outbreak risk and contribute to the One Health approach for the prevention and control of CCHF disease.

基因组分割对病毒基因表达控制和RNA组装具有重要意义。它还创造了重新分类的潜力：共同感染同一细胞的病毒之间完整基因片段的交换。重新分类与重组不同，因为它允许许多不同的基因型从单个共感染的细胞中出现。分割不仅可以增强遗传多样化，而且由于很少有重新分类在人口规模上成功的情况，它在分割病毒的进化史上起着独特的作用。 ngari病毒是新型病毒出现的Bunyaviridae家族的一个显着例子。对于流感A（IAV），最有特征的分段病毒，保证促进了1957年，1968年和2009年的流行病菌株的形成。在WHO 2018 R＆D Blueprint的七种流行性疾病中，在7种流行性疾病中，急需的公共健康紧急情况，是迫切需要的，迫切需要加速研究。出血发烧。因此，该项目的总体假设是，分割病毒的重新分类不仅在推动其多样化和进化方面发挥了重要作用，而且还可以极大地改变其生态学和传播动态。 Specifically, we aim to 1) develop mathematical models of the intracellular life cycle for a family of segmented viruses to quantify for the first time their viral replication dynamics and reassortment frequencies, and 2) develop standardised sequencing protocols and novel phylogenetic methods to quantify the evolutionary and epidemiological implications of reassortment for Crimean-Congo hemorrhagic fever virus (CCHFV).该项目将建立来自土耳其和塔吉克斯坦CCHFV流行地区的临床和现场样品的生物库。临床和现场数据将被利用，以确保我们的方法和结果有可能为公共卫生策略提供信息，预测爆发风险并有助于预防和控制CCHF疾病的一种健康方法。