In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity.
In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity.
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DOI：
10.1016/j.virol.2011.10.006
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发表时间：
2012-01-05
期刊：
影响因子：
3.7
通讯作者：
Donis RO
中科院分区：
文献类型：
--
作者：
Chen LM;Blixt O;Stevens J;Lipatov AS;Davis CT;Collins BE;Cox NJ;Paulson JC;Donis RO
α2-3特异性高致病性禽流感病毒（H5N1）获得α2-6唾液酸受体特异性被认为是在人类中有效传播的先决条件。通过体外选择结合 α2-6 唾液酸苷，我们鉴定了四种在血凝素中具有氨基酸取代的变异病毒（S227N、D187G、E190G 和 Q196R），通过聚糖阵列分析显示，α2-6 结合略有增加，α2-3 结合略有减少。然而，将 Q196R 与先前大流行病毒（Q226L 和 G228S）的突变相结合的突变病毒显示主要与 α2-6 结合。与野生型 H5N1 不同，这种突变病毒在雪貂模型中是通过直接接触传播的，但不是通过空气中的呼吸道飞沫传播的。然而，带有突变血凝素、人类 N2 神经氨酸酶和 H5N1 病毒内部基因的重配病毒部分通过呼吸道飞沫传播。雪貂空气传播能力所需的复杂变化表明，H5N1 病毒在人类中的传播能力需要广泛的进化。
Acquisition of α2-6 sialoside receptor specificity by α2-3 specific highly-pathogenic avian influenza viruses (H5N1) is thought to be a prerequisite for efficient transmission in humans. By in vitro selection for binding α2-6 sialosides, we identified four variant viruses with amino acid substitutions in the hemagglutinin (S227N, D187G, E190G, and Q196R) that revealed modestly increased α2-6 and minimally decreased α2-3 binding by glycan array analysis. However, a mutant virus combining Q196R with mutations from previous pandemic viruses (Q226L and G228S) revealed predominantly α2-6 binding. Unlike the wild type H5N1, this mutant virus was transmitted by direct contact in the ferret model although not by airborne respiratory droplets. However, a reassortant virus with the mutant hemagglutinin, a human N2 neuraminidase and internal genes from an H5N1 virus was partially transmitted via respiratory droplets. The complex changes required for airborne transmissibility in ferrets suggest that extensive evolution is needed for H5N1 transmissibility in humans.