Pathogenicity and transmissibility of North American triple reassortant swine influenza A viruses in ferrets.
Pathogenicity and transmissibility of North American triple reassortant swine influenza A viruses in ferrets.
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DOI：
10.1371/journal.ppat.1002791
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发表时间：
2012
期刊：
影响因子：
6.7
通讯作者：
Webby RJ
中科院分区：
文献类型：
--
作者：
Barman S;Krylov PS;Fabrizio TP;Franks J;Turner JC;Seiler P;Wang D;Rehg JE;Erickson GA;Gramer M;Webster RG;Webby RJ
自2005年以来，北美三重重组猪（TRS）甲型流感病毒引起了零星的人间感染，但没有记录到人与人之间的传播。这些病毒有6个基因片段（PB2、PB1、PA、HA、NP和NS）与2009年H1N1大流行病毒密切相关。因此，了解这些病毒的致病性和传播性可能有助于确定2009年H1N1大流行病毒的毒力决定因素，并阐明TRS病毒对人类健康构成的潜在威胁。本研究在雪貂模型中评估了三组含有猪样和/或人样HA和NA基因片段的北美TRS病毒的致病性和传播性。该研究的目的仅是检测这三组病毒的传播性和致病性的信息和重要模式。我们观察到，无论其HA和NA谱系如何，TRS病毒在雪貂中具有中等致病性，并且在上呼吸道和下呼吸道都能有效地生长。研究的所有北美TRS病毒都是通过直接接触在雪貂之间传播的。但其经呼吸道飞沫传播的能力与其HA和NA谱系有关：具有人样HA和NA的TRS病毒传播效率最高，具有猪样HA和NA的TRS病毒传播最低或不传播，具有猪样HA和人样NA （N2）的TRS病毒传播能力中等。我们得出结论，HA和NA的谱系可能在这些病毒的呼吸道飞沫传播中起关键作用。这些发现对大流行规划具有重要意义，值得确认。北美三重重组猪（TRS）甲型流感病毒已引起散发的人感染，但尚未确定人与人之间的传播。我们希望阐明TRS病毒对人类健康构成的潜在威胁，并确定TRS病毒和密切相关的2009年H1N1大流行病毒的毒力决定因素。我们采用雪貂模型，用猪病毒和人病毒的HA和NA抗原蛋白评价北美TRS病毒的致病性和传播性。我们观察到，北美TRS病毒在雪貂的上呼吸道和下呼吸道都能有效地生长，并对雪貂产生中等致病性。无论其HA和NA谱系如何，这些病毒都很容易通过直接接触传播。然而，当病毒携带人类甲型流感病毒的HA和NA而不是猪甲型流感病毒时，通过呼吸道飞沫传播的可能性要大得多。由于雪貂是人类流感感染的有用模型，这一发现有助于预测增加人类健康风险的特征。
North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections since 2005, but human-to-human transmission has not been documented. These viruses have six gene segments (PB2, PB1, PA, HA, NP, and NS) closely related to those of the 2009 H1N1 pandemic viruses. Therefore, understanding of these viruses' pathogenicity and transmissibility may help to identify determinants of virulence of the 2009 H1N1 pandemic viruses and to elucidate potential human health threats posed by the TRS viruses. Here we evaluated in a ferret model the pathogenicity and transmissibility of three groups of North American TRS viruses containing swine-like and/or human-like HA and NA gene segments. The study was designed only to detect informative and significant patterns in the transmissibility and pathogenicity of these three groups of viruses. We observed that irrespective of their HA and NA lineages, the TRS viruses were moderately pathogenic in ferrets and grew efficiently in both the upper and lower respiratory tracts. All North American TRS viruses studied were transmitted between ferrets via direct contact. However, their transmissibility by respiratory droplets was related to their HA and NA lineages: TRS viruses with human-like HA and NA were transmitted most efficiently, those with swine-like HA and NA were transmitted minimally or not transmitted, and those with swine-like HA and human-like NA (N2) showed intermediate transmissibility. We conclude that the lineages of HA and NA may play a crucial role in the respiratory droplet transmissibility of these viruses. These findings have important implications for pandemic planning and warrant confirmation. North American triple reassortant swine (TRS) influenza A viruses have caused sporadic human infections, but human-to-human transmission has not been established. We wished to elucidate potential human health threats posed by the TRS viruses and to identify determinants of virulence in the TRS and closely related 2009 H1N1 pandemic viruses. We used a ferret model to evaluate the pathogenicity and transmissibility of North American TRS viruses with the HA and NA antigenic proteins of swine viruses and of human viruses. We observed that the North American TRS viruses grew efficiently in both the upper and lower respiratory tracts and caused moderate pathogenicity in ferrets. The viruses were readily transmissible via direct contact, irrespective of their HA and NA lineages. However, transmissibility via respiratory droplets was substantially greater when the viruses carried the HA and NA of human influenza A viruses rather than of swine influenza A viruses. Because ferrets are a useful model of human influenza infection, this finding helps to predict features that increase the risk to human health.
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影响因子：
6.7
作者：
Lakdawala SS;Lamirande EW;Suguitan AL Jr;Wang W;Santos CP;Vogel L;Matsuoka Y;Lindsley WG;Jin H;Subbarao K
通讯作者：
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作者：
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通讯作者：
Subbarao K
影响因子：
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通讯作者：
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