In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity
In Vitro Assessment of Attachment Pattern and Replication Efficiency of H5N1 Influenza A Viruses with Altered Receptor Specificity
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DOI：
10.1128/jvi.02737-09
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
de Wit, Emmie
中科院分区：
文献类型：
--
作者：
Chutinimitkul, Salin;van Riel, Debby;de Wit, Emmie
H5N1型高致病性禽流感病毒的持续传播引起了极大关注。这种病毒可能获得人类甲型流感病毒受体α 2,6-链唾液酸（SA）的特异性，并能够在人类之间有效传播，这是对人类健康的持续威胁。不同的研究描述了临床高致病性H5N1分离株的血凝素（HA）中的氨基酸置换，或实验引入的氨基酸置换导致这些病毒株与α 2,6-链SA的结合增加，但不是唯一的结合。我们将所有先前描述的氨基酸替换及其组合引入单一遗传背景，流感病毒a/印度尼西亚/5/05 HA，并测试了这27个突变病毒的受体特异性。然后确定具有α 2,6-连接SA受体偏好的病毒对雪貂和人类上呼吸道和下呼吸道组织的附着模式，并将其与人类甲型流感病毒（H3N2）的附着模式进行比较。至少有三种突变病毒显示出与人类H3N2病毒相似的对人类呼吸道的附着模式。接下来，确定了这些突变病毒的复制效率以及三种不同的神经氨酸酶对病毒复制的影响。这些数据表明，流感病毒A/Indonesia/5/05可能只需要一个氨基酸替换就能获得人受体特异性，同时保持复制能力，因此表明高致病性H5N1造成的大流行威胁远未减弱。
The continuous circulation of the highly pathogenic avian influenza (HPAI) H5N1 virus has been a cause of great concern. The possibility of this virus acquiring specificity for the human influenza A virus receptor, alpha 2,6-linked sialic acids (SA), and being able to transmit efficiently among humans is a constant threat to human health. Different studies have described amino acid substitutions in hemagglutinin (HA) of clinical HPAI H5N1 isolates or that were introduced experimentally that resulted in an increased, but not exclusive, binding of these virus strains to alpha 2,6-linked SA. We introduced all previously described amino acid substitutions and combinations thereof into a single genetic background, influenza virus A/Indonesia/5/05 HA, and tested the receptor specificity of these 27 mutant viruses. The attachment pattern to ferret and human tissues of the upper and lower respiratory tract of viruses with alpha 2,6-linked SA receptor preference was then determined and compared to the attachment pattern of a human influenza A virus (H3N2). At least three mutant viruses showed an attachment pattern to the human respiratory tract similar to that of the human H3N2 virus. Next, the replication efficiencies of these mutant viruses and the effects of three different neuraminidases on virus replication were determined. These data show that influenza virus A/Indonesia/5/05 potentially requires only a single amino acid substitution to acquire human receptor specificity, while at the same time remaining replication competent, thus suggesting that the pandemic threat posed by HPAI H5N1 is far from diminished.