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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Minimal molecular constraints for respiratory droplet transmission of an avian- human H9N2 influenza A virus
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Minimal molecular constraints for respiratory droplet transmission of an avian- human H9N2 influenza A virus

机译:禽-人H9N2甲型流感病毒呼吸道飞沫传播的最小分子限制

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摘要

Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian-human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.
机译:大流行性流感需要一种新的血凝素(HA)亚型在种间传播流感病毒,该亚型可通过重组或点突变适应其新宿主,并通过雾化的呼吸道飞沫传播。 1957年和1968年的前两次大流行是由于低致病性禽流感病毒和该时期人类亚型的重排造成的。然而,导致大流行病毒的条件仍然知之甚少。考虑到欧亚大陆具有人类样受体特异性的禽类H9N2流感的流行情况,以及偶发性禽流感向人和猪的传播,我们想确定禽类-人类H9N2重配株在哺乳动物动物模型(雪貂)中是否可以通过呼吸道传播。在这里,我们显示了在雪貂中适应后,在人类H3N2骨架中携带禽H9N2表面蛋白的重配病毒可以通过呼吸道飞沫有效传播,从而产生类似于人类流感感染的临床感染。在这种能够呼吸小滴传播的病毒中,蛋白质水平的变化很小。仅表达适应雪貂的病毒的HA和神经氨酸酶(NA)的重配病毒能够解释其传播性,这表明在通过重配获得所有人类病毒内部基因后,目前正在传播的禽类H9N2病毒在哺乳动物中几乎不需要适应。血凝素抑制(HI)分析表明该病毒的抗原特性发生了变化,这对制备针对禽H9N2流感的疫苗种子备有深远的意义。该报告说明雾化呼吸道传播并非仅针对当前的人类H1,H2和H3流感亚型。

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  • 作者单位

    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742;

    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742 Molecular, Virology, and Vaccines Branch, Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333;

    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742;

    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742 Synbiotics Corporation, 8075 Greenmead Drive, College Park, MD 20742;

    Department of Veterinary Medicine, University of Maryland, College Park, and Virginia-Maryland Regional College of Veterinary Medicine, 8075 Greenmead Drive, College Park, MD 20742;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    aerosol; ferrets; contact; pandemic; preparedness;

    机译:气雾剂;雪貂联系;大流行;准备;

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