Recognition of N-glycolylneuraminic acid linked to galactose by the α2,3 linkage is associated with intestinal replication of influenza A virus in ducks

Recognition of N-glycolylneuraminic acid linked to galactose by the α2,3 linkage is associated with intestinal replication of influenza A virus in ducks
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DOI:
10.1128/jvi.74.19.9300-9305.2000
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发表时间:
2000-10-01
影响因子:
5.4
通讯作者:
Kawaoka, Y
Kawaoka, Y
中科院分区:
医学2区
文献类型:
--
作者:
Ito, T;Suzuki, Y;Kawaoka, Y

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H3型人流感病毒的血凝素(IU)不支持病毒在鸭肠中的复制,尽管它起源于禽类。人A/Udorn/307/72 (H3N2) HA 226位的Leu-to-Gin突变和228位的Ser-to-Gly突变允许重组病毒[人Udorn HA,与来自A/绿头鸭/New York/6750/78 (H2N2)的所有其他基因]在鸭子中复制。为了了解这种宿主范围限制变化的分子基础,我们研究了鸭流感病毒以及人鸭病毒重组的受体特异性。结果表明,鸭肠中含有n -糖神经酸(NeuGc)的糖缀合物片段(NeuGc α 2,3 gal)与半乳糖通过α 2,3连锁连接(NeuGc α 2,3 gal)的识别与病毒复制有关。用NeuGc α 2,3gal特异性抗血清进行免疫荧光检测,主要在鸭结肠隐窝上皮细胞上检测到该片段。这种识别,加上隐窝细胞中NeuGc的生化证据,与病毒在鸭结肠中复制的能力完全相关。这些结果表明,NeuGc α 2,3- gal片段的识别在禽流感病毒的亲肠性中起重要作用。
The hemagglutinin (IU) of H3 human influenza viruses does not support viral replication in duck intestine despite its avian origin. A Leu-to-Gin mutation at position 226 and a Ser-to-Gly mutation at position 228 in the HA of human A/Udorn/307/72 (H3N2) permit a reassortant virus [human Udorn HA, with all other genes from A/mallard/New York/6750/78 (H2N2)] to replicate in ducks. To understand the molecular basis of this change in host range restriction, we investigated the receptor specificity of duck influenza viruses as well as of human-duck virus reassortants. The results indicate that the recognition of a glycoconjugate moiety possessing N-glycolneuramic acid (NeuGc) linked to galactose by the alpha 2,3 linkage (NeuGc alpha 2,3Gal) is associated with viral replication in duck intestine. Immunofluorescence assays with NeuGc alpha 2,3Gal-specific antiserum detected this moiety primarily on the crypt epithelial cells of duck colon. Such recognition, together with biochemical evidence of NeuGc in crypt cells, correlated exactly with the ability of the virus to replicate in duck colon. These results suggest that recognition of the NeuGc alpha 2,3-Gal moiety plays an important role in the enterotropism of avian influenza viruses.