Influenza Viral Genomics and Evolution

流感病毒基因组学和进化

• 批准号: 8336220
• 负责人: Jeffery Taubenberger
• 金额: $ 63.42万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8336220
• 关键词: American; Animals; Antiviral Agents; Avian Influenza A Virus; Biological Assay; Biology; Birds; Cessation of life; Complex; DNA; Data; Detection; Diagnosis; Diagnostic; Dideoxy Chain Termination DNA Sequencing; Disease Outbreaks; Domestic Animals; Domestic Fowls; Ecology; Epidemic; Equus caballus; European; Evolution; Family suidae; Flying body movement; Genes; Genomics; Geographic Locations; Goals; Human; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H3N2 Subtype; Influenza A Virus, H5N1 Subtype; Influenza A virus; Minor Groove; Molecular; Molecular Diagnostic Testing; Morbidity - disease rate; Natural History; Pathogenicity; Pharmacotherapy; Population; Porcine Influenza A Virus; Sampling; Seasons; Sentinel; Site; Time; Vaccines; Viral; Virus; base; influenza epidemic; influenzavirus; insight; mortality; next generation; pandemic disease; pandemic influenza; pandemic preparedness; pathogen; wild bird

Influenza A viruses (IAV) are significant human pathogens causing yearly epidemics and occasional pandemics. Past pandemics have resulted in significant morbidity and mortality. The 1918 influenza pandemic was thought to have resulted in the death of at least 675,000 people in the U.S., and 40 million people worldwide. Annual influenza A virus epidemics are also very significant, resulting in approximately 30,000 deaths in the U.S. per year. Pandemic strains of influenza emerge periodically and are thought to be derived ultimately from avian influenza A viruses. The current 2009 pandemic influenza virus emerged by reassortment of two pre-existing swine influenza virus lineages. The first lineage is the European avian-like swine lineage which emerged from an avian influenza virus in toto. The second lineage is the triple-reassortant H1N2 swine influenza virus containing gene segments derived from avian, human, and classical swine influenza viruses. The natural reservoir of influenza A viruses is thought to be wild waterfowl. Genetically and antigenically diverse influenza A viruses circulate in wild birds and viral strains from this pool can adapt to new hosts, including humans and domestic animals. Influenza A viruses are also significant pathogens for agriculturally important animals like poultry, swine, and horses. Understanding the mechanisms of host switching are very important for surveillance and pandemic preparedness. Understanding the molecular basis underlying the annual evolution of human influenza will aid in vaccine strain selection. Avian influenza A virus evolutionary biology: We evaluated the molecular epizootology of approximately 50 avian influenza viruses isolated from the same population of birds over a several month period in 2006. Low pathogenicity avian influenza viruses of both H5N1 and H7N3 subtypes were isolated. These subtypes have been associated with highly pathogenic avian influenza virus outbreaks. From August 2 to October 11, 2006, clusters of low pathogenicity (LP) North American lineage H5N1 and H7N3 avian influenza A viruses (AIV), and other subtypes, were recovered from free-flying, resident, wild mallards used as sentinels at one site. The antigenic subtypes, pathogenicity potential, and Sanger sequencing of the isolates determined the H5N1 and H7N3 isolates were only recovered from samples collected on 8/2/2006 and 9/8/2006, respectively. However, subsequent efforts using next-generation sequencing (NGS) and additional Sanger sequencing found partial H7 segments in other HA-NA virus combinations on 8/2/2006, 9/8/2006 and 10/11/2006. It is well established that over larger geographic areas and years AIVs form transient genomic constellations; this sequential sampling data revealed that over a short period of time the dynamics of AIVs can be active and newer sequencing platforms increase recognition of mixed infections. Both findings provide further insight into the natural history of AIVs in natural reservoirs. Despite the emergence of the pandemic H1N1 influenza A virus in 2009, seasonal H3N2 viruses continue to co-circulate in the population and may even predominate in coming influenza seasons. Because rapid subtype-specific diagnosis is often warranted to guide antiviral drug therapy, we developed a rapid molecular diagnostic test involving a specific minor groove binder TaqMan assay for H3N2 viruses with a detection limit of 16.5 standard DNA copies.

流感病毒（IAV）是重要的人类病原体，导致年度流行病和偶尔大流行病。过去的大流行病导致了明显的发病率和死亡率。人们认为，1918年的流感大流行导致了美国至少有67.5万人死亡，全世界有4000万人死亡。年度流感病毒流行病也非常重要，每年在美国大约30,000人死亡。流感的大流行菌株定期出现，被认为最终来自禽流感病毒。当前的2009年大流行性流感病毒是通过重新分类的两个先前存在的猪流感病毒谱系而出现的。第一个谱系是欧洲类似鸟类的猪谱系，它来自Toto的禽流感病毒。第二个谱系是含有源自鸟类，人类和经典猪流感病毒的基因段的三倍体H1N2猪流感病毒。流感的天然水库被认为是野生水禽。从遗传和抗原上多样化的流感病毒在野生鸟类中循环，该池的病毒菌株可以适应新宿主，包括人类和家畜。流感病毒也是农业重要动物（如家禽，猪和马）的重要病原体。了解宿主切换的机制对于监视和大流行准备非常重要。了解人类流感的年度演变的分子基础将有助于疫苗菌株的选择。 禽流感病毒进化生物学：我们评估了2006年从同一鸟类中分离出的大约50种鸟类流感病毒的分子膨胀学。这些亚型与高致病性禽流感病毒暴发有关。 从2006年8月2日至10月11日，从一个地点用作自由飞行，居住的，野生的野兽，从一个地点使用自由飞行，居民，野生野兽，从一个地点中回收了低致病性（LP）北美谱系H5N1和H7N3 Avian流感病毒（AIV）和其他亚型。分离株的抗原亚型，致病性和Sanger测序分别从2006年8月2日和9/8/2006收集的样品中回收了H5N1和H7N3分离株。但是，随后使用下一代测序（NGS）和其他Sanger测序的努力发现了在2006年8月2日，2006年9月8日和2006年10月11日的其他HA-NA病毒组合中的部分H7段。众所周知，在较大的地理区域和多年中，AIV形成了瞬态基因组星座。该顺序抽样数据表明，在短时间内，AIV的动力学可以是活跃的，而更新的测序平台会增加对混合感染的识别。这两种发现都可以进一步了解自然储层中AIV的自然历史。 尽管2009年出现了大流行的H1N1流感病毒，但季节性的H3N2病毒仍在人口中继续循环，甚至可能在即将到来的流感季节中占主导地位。由于通常有必要快速的亚型特异性诊断来指导抗病毒药物治疗，因此我们开发了一种快速的分子诊断测试，涉及针对H3N2病毒的特定次要凹槽粘合剂Taqman分析，其检测极限为16.5标准DNA拷贝。