Analysis of Historical Influenza Viruses

历史流感病毒分析

• 批准号: 9354810
• 负责人: Jeffery Taubenberger
• 金额: $ 26.49万
• 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/9354810
• 关键词: Archives; Autopsy; Bacterial Infections; Bacterial RNA; Birds; Cells; Cessation of life; Development; Disease; Disease Outbreaks; Epidemic; Evolution; Family suidae; Formalin; Future; Genes; Goals; Hemagglutinin; Human; In Vitro; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Influenza A virus; Medical; Methods; Modeling; Molecular; Morbidity - disease rate; Paraffin Embedding; Pathology; Phylogenetic Analysis; Pneumonia; Public Health; RNA; Reassortant Viruses; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal RNA; Sequence Analysis; Source; Specificity; Tissue Sample; Tissues; Variant; Viral; Virulence; Virulent; Virus; base; deep sequencing; epizootic; influenza outbreak; influenzavirus; mRNA Expression; mortality; novel; pandemic disease; pandemic influenza; pandemic preparedness; pathogen; receptor; seasonal influenza; viral RNA

Influenza A viruses 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 50 million people worldwide. Pandemics in 1957 and 1968, while less severe, were also of major public health importance. In 2009, a novel pandemic emerged and caused up to 18,000 deaths in the U.S. and up to 575,000 deaths globally. Understanding the molecular basis for the formation of pandemic influenza strains is critical. The 1957 and 1968 pandemics were human-avian reassortant viruses in which two or three influenza gene segments from the then circulating human influenza viruses were replaced with genes from an avian source. The 2009 pandemic virus arose via reassortment between two swine-adapted influenza viruses. Sequence and phylogenetic analysis of the 1918 pandemic virus suggested that it was derived from an avian-like virus possibly via an intermediate host in the decade before the pandemic. The 1918 pandemic virus caused several epidemiologically distinct waves. The so-called first wave, in the summer months of 1918, may have represented an early form of the more virulent second wave. To understand how this pandemic virus emerged and to model its virulence, it is important to place this virus in the context of human influenza viruses circulating before 1918 and to follow the early evolution of human H1N1 viruses after 1918. Because human influenza isolates are not available earlier than 1933, the only way to characterize these viruses is by identification of influenza RNA fragments preserved in formalin-fixed, paraffin-embedded autopsy tissues. Efforts to identify pre-1918 influenza virus RNA-positive autopsy material are continuing. Possible fatal influenza pneumonia cases from 1907-1917 have been identified in tissue archives and anonymized materials are being screened for host and viral RNA by RT-PCR. In a related effort, a method has been developed allowing high-throughput deep sequencing of host, viral, and bacterial RNA from archival tissue samples. This method significantly reduces ribosomal RNA allowing sequence analysis of viral and host mRNA expression and identification of secondary bacterial infections. Lastly, receptor specificity of variant 1918 influenza A virus hemagglutinins was evaluated in vitro in primary human airway cells.

流感病毒是重要的人类病原体，导致年度流行病和偶尔出现。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年流感大流行导致了美国至少有67.5万人死亡，全球5000万人死亡。 1957年和1968年的大流行学虽然不太严重，但也具有重要的公共健康重要性。 2009年，美国出现了一个新颖的大流行，在美国造成了多达18,000人死亡，全球高达57.5万人死亡。了解大流行性流感菌株形成的分子基础至关重要。 1957年和1968年的大流行病是人类育种的替代病毒，其中当时循环的人类流感病毒的两个或三个流感基因段被来自禽源物的基因代替。 2009年的大流行病毒是通过在两个适应猪的流感病毒之间的重新分类而产生的。 1918年大流行病毒的序列和系统发育分析表明，它是在大流行前十年中通过中间宿主衍生出来的。 1918年的大流行病毒引起了几种流行病学上不同的波。所谓的第一波在1918年的夏季可能代表了更毒的第二波形式。 要了解这种大流行病毒是如何出现并模仿其毒力的，将该病毒放在1918年之前循环的人类流感病毒的背景下，遵循1918年后的人类H1N1病毒的早期演变。石蜡包裹的尸检组织。 识别1918年前的流感病毒RNA阳性尸检材料的努力正在继续。从1907 - 1917年开始，在组织档案中发现了可能的致命流感肺炎病例，RT-PCR正在筛选匿名材料以供宿主和病毒RNA筛选。在相关的工作中，已经开发了一种方法，允许对档案组织样品的宿主，病毒和细菌RNA进行高通量的深度测序。 该方法显着降低了核糖体RNA，允许对病毒和宿主mRNA表达的序列分析以及二次细菌感染的鉴定。 最后，在原发性人类气道细胞中评估了1918年流感的变体的受体特异性。