A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission
A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission
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DOI：
10.1126/science.1136212
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发表时间：
2007-02-02
期刊：
影响因子：
56.9
通讯作者：
Garcia-Sastre, Adolfo
中科院分区：
文献类型：
--
作者：
Tumpey, Terrence M.;Maines, Taronna R.;Garcia-Sastre, Adolfo
1918年流感大流行是一系列灾难性的病毒爆发，蔓延到全球。在这里，我们表明，只有1918年流感血凝素受体结合位点的轻微变化才能改变这种大流行病毒的传播性。两个氨基酸突变导致受体结合偏好从人的α-2，6转换为禽α-2，3唾液酸，导致病毒不能在雪貂之间传播呼吸道飞沫，但保持了其在上呼吸道的致命性和复制效率。此外，1918年具有双重α-2，6和α-2，3特异性的病毒的传播很差，这表明主要的人类α-2，6唾液酸结合偏好对于这种大流行病毒的最佳传播至关重要。这些发现证实了血凝素受体特异性在哺乳动物间流感病毒传播中的重要作用。
The 1918 influenza pandemic was a catastrophic series of virus outbreaks that spread across the globe. Here, we show that only a modest change in the 1918 influenza hemagglutinin receptor binding site alters the transmissibility of this pandemic virus. Two amino acid mutations that cause a switch in receptor binding preference from the human alpha-2,6 to the avian alpha-2,3 sialic acid resulted in a virus incapable of respiratory droplet transmission between ferrets but that maintained its lethality and replication efficiency in the upper respiratory tract. Furthermore, poor transmission of a 1918 virus with dual alpha-2,6 and alpha-2,3 specificity suggests that a predominant human alpha-2,6 sialic acid binding preference is essential for optimal transmission of this pandemic virus. These findings confirm an essential role of hemagglutinin receptor specificity for the transmission of influenza viruses among mammals.