A Polymorphism in the Hemagglutinin of the Human Isolate of a Highly Pathogenic H5N1 Influenza Virus Determines Organ Tropism in Mice
A Polymorphism in the Hemagglutinin of the Human Isolate of a Highly Pathogenic H5N1 Influenza Virus Determines Organ Tropism in Mice
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DOI：
10.1128/jvi.00850-10
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发表时间：
2010-08-15
影响因子：
5.4
通讯作者：
Schwemmle, Martin
中科院分区：
文献类型：
--
作者：
Maenz, Benjamin;Matrosovich, Mikhail;Schwemmle, Martin
我们表征了编码血凝素（HA）的人H5 N1病毒分离株（KAN-1），所述血凝素（HA）在氨基酸位置222处具有K至E取代，所述HA先前描述为在感染患者的肺中选择。在小鼠中，HA（222 E）编码病毒的生长主要局限于肺，但回复到222 K允许病毒扩散到大脑。与HA（222 K）相比，HA（222 E）变体对合成Neu 5Ac 2 - 3Gal末端受体类似物的结合亲和力总体降低，但一种类似物除外[Neu 5Ac α 2-3Gal β 1-4（Fuc α 1-3）（6-HSO 3）GlcNAc β，Su-SLe（x）]。我们的研究结果表明，H5 N1病毒HA的人源性突变可以影响病毒的复制效率和器官嗜性。
We characterized a human H5N1 virus isolate (KAN-1) encoding a hemagglutinin (HA) with a K-to-E substitution at amino acid position 222 that was previously described to be selected in the lung of the infected patient. In mice, the growth of the HA(222E)-encoding virus was mainly confined to the lung, but reversion to 222K allowed virus to spread to the brain. The HA(222E) variant showed an overall reduced binding affinity compared to that of HA(222K) for synthetic Neu5Ac2-3Gal-terminated receptor analogues, except for one analogue [Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)(6-HSO3) GlcNAc beta, Su-SLe(x)]. Our results suggest that human-derived mutations in HA of H5N1 viruses can affect viral replication efficiency and organ tropism.