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混合感染与流感病毒多样性的起源

Mixed infection and the genesis of influenza virus diversity.

作者信息

Ghedin Elodie, Fitch Adam, Boyne Alex, Griesemer Sara, DePasse Jay, Bera Jayati, Zhang Xu, Halpin Rebecca A, Smit Marita, Jennings Lance, St George Kirsten, Holmes Edward C, Spiro David J

机构信息

University of Pittsburgh School of Medicine, Department of Medicine, Pittsburgh, Pennsylvania 15261, USA.

出版信息

J Virol. 2009 Sep;83(17):8832-41. doi: 10.1128/JVI.00773-09. Epub 2009 Jun 24.

Abstract

The emergence of viral infections with potentially devastating consequences for human health is highly dependent on their underlying evolutionary dynamics. One likely scenario for an avian influenza virus, such as A/H5N1, to evolve to one capable of human-to-human transmission is through the acquisition of genetic material from the A/H1N1 or A/H3N2 subtypes already circulating in human populations. This would require that viruses of both subtypes coinfect the same cells, generating a mixed infection, and then reassort. Determining the nature and frequency of mixed infection with influenza virus is therefore central to understanding the emergence of pandemic, antigenic, and drug-resistant strains. To better understand the potential for such events, we explored patterns of intrahost genetic diversity in recently circulating strains of human influenza virus. By analyzing multiple viral genome sequences sampled from individual influenza patients we reveal a high level of mixed infection, including diverse lineages of the same influenza virus subtype, drug-resistant and -sensitive strains, those that are likely to differ in antigenicity, and even viruses of different influenza virus types (A and B). These results reveal that individuals can harbor influenza viruses that differ in major phenotypic properties, including those that are antigenically distinct and those that differ in their sensitivity to antiviral agents.

摘要

对人类健康可能造成毁灭性后果的病毒感染的出现,在很大程度上取决于其潜在的进化动态。禽流感病毒(如A/H5N1)进化为能够在人际间传播的病毒的一种可能情况是,从已在人群中传播的A/H1N1或A/H3N2亚型获取遗传物质。这将要求这两种亚型的病毒共同感染同一细胞,形成混合感染,然后进行重配。因此,确定流感病毒混合感染的性质和频率对于理解大流行、抗原性和耐药性毒株的出现至关重要。为了更好地理解此类事件的可能性,我们探索了近期流行的人类流感病毒株的宿主内遗传多样性模式。通过分析从个体流感患者身上采集的多个病毒基因组序列,我们发现了高水平的混合感染,包括同一流感病毒亚型的不同谱系、耐药和敏感毒株、抗原性可能不同的毒株,甚至不同流感病毒类型(A和B)的病毒。这些结果表明,个体可能携带主要表型特性不同的流感病毒,包括抗原性不同的病毒以及对抗病毒药物敏感性不同的病毒。

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