Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium.
Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium.
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DOI：
10.1371/journal.pone.0007836
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发表时间：
2009-11-18
期刊：
影响因子：
3.7
通讯作者：
Barclay WS
中科院分区：
文献类型：
--
作者：
Ayora-Talavera G;Shelton H;Scull MA;Ren J;Jones IM;Pickles RJ;Barclay WS
2009年出现的猪源H1N1流感病毒是21世纪世纪的第一次大流行，及时提醒人们流感病毒对国际公共卫生的影响，即使是那些与轻度疾病有关的流感病毒。高致病性H5N1流感病毒在禽类中的广泛分布引起了人们对它可能引起人类流感大流行的担忧。与偶尔人类感染H5N1病毒相关的死亡率接近60%，这表明H5N1大流行将对全球健康和经济造成破坏。迄今为止，H5N1病毒尚未获得在人类之间有效传播的倾向。这背后的原因尚不清楚，特别是考虑到与流感病毒复制相关的高突变率。在此，我们使用一组重组H5血凝素（HA）变体来证明H5 HA结合人气道上皮细胞的潜力，气道上皮细胞是流感病毒感染和传播的主要靶组织。虽然亲本H5 HA表现出与人气管上皮的有限结合，但引入选定的突变将结合特征转化为当前人流感病毒株HA的结合特征。引人注目的是，这些氨基酸的变化需要在自然发生的H5分离株的基因组中同时发生多个突变。此外，携带中间序列的H5 HA不能结合气道组织，并且可能代表进化“死胡同”的突变。我们的结论是，虽然可以证明H5适应人类气道的遗传变化，但它们可能不会在自然病毒复制过程中容易出现。这种遗传障碍限制了目前H5病毒引起人类大流行的可能性。
The emergence in 2009 of a swine-origin H1N1 influenza virus as the first pandemic of the 21st Century is a timely reminder of the international public health impact of influenza viruses, even those associated with mild disease. The widespread distribution of highly pathogenic H5N1 influenza virus in the avian population has spawned concern that it may give rise to a human influenza pandemic. The mortality rate associated with occasional human infection by H5N1 virus approximates 60%, suggesting that an H5N1 pandemic would be devastating to global health and economy. To date, the H5N1 virus has not acquired the propensity to transmit efficiently between humans. The reasons behind this are unclear, especially given the high mutation rate associated with influenza virus replication. Here we used a panel of recombinant H5 hemagglutinin (HA) variants to demonstrate the potential for H5 HA to bind human airway epithelium, the predominant target tissue for influenza virus infection and spread. While parental H5 HA exhibited limited binding to human tracheal epithelium, introduction of selected mutations converted the binding profile to that of a current human influenza strain HA. Strikingly, these amino-acid changes required multiple simultaneous mutations in the genomes of naturally occurring H5 isolates. Moreover, H5 HAs bearing intermediate sequences failed to bind airway tissues and likely represent mutations that are an evolutionary “dead end.” We conclude that, although genetic changes that adapt H5 to human airways can be demonstrated, they may not readily arise during natural virus replication. This genetic barrier limits the likelihood that current H5 viruses will originate a human pandemic.
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