Adaptation of a Duck Influenza A Virus in Quail
Adaptation of a Duck Influenza A Virus in Quail
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DOI：
10.1128/jvi.06100-11
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发表时间：
2012-02-01
影响因子：
5.4
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
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作者：
Yamada, Shinya;Shinya, Kyoko;Kawaoka, Yoshihiro
鹌鹑被认为是水生鸟类和陆生鸟类（例如鸡）之间甲型流感病毒的中间宿主，因为它们对水生鸟类病毒高度敏感，然后适应在新宿主中有效复制。然而，水禽流感病毒在鹌鹑中的复制是否同样会导致其在人类中的有效复制？使用唾液酸-半乳糖连接特异性凝集素，我们在鹌鹑的气管细胞上发现了禽类（唾液酸低聚糖上的唾液酸-α 2-3-半乳糖[Sia α 2-3Gal]连接）和人类（Sia α 2-6Gal）型受体，与之前的报道一致。我们还在鹌鹑体内传代了鸭 H3N2 病毒 19 次。序列分析显示，在这些传代过程中，血凝素（HA）中积累了八个突变。有趣的是，在适应病毒中发现的许多改变的HA氨基酸存在于人类季节性病毒中，但不存在于鸭病毒中。我们还发现传代过程中神经氨酸酶的茎逐步缺失，导致神经氨酸酶功能降低。尽管受体结合袋附近有一些血凝素突变，但没有检测到受体特异性的明显变化。然而，反向遗传学产生的具有鹌鹑传代病毒的血凝素和神经氨酸酶的病毒在正常人支气管上皮细胞中的复制明显优于具有亲本HA和神经氨酸酶的病毒，而在鸭细胞中没有观察到两种病毒之间的复制存在显着差异。此外，鹌鹑传代病毒而非原始鸭病毒在人支气管上皮细胞中复制。这些数据表明鹌鹑可以作为水禽流感病毒传播给人类的中间宿主。
Quail are thought to serve as intermediate hosts of influenza A viruses between aquatic birds and terrestrial birds, such as chickens, due to their high susceptibility to aquatic-bird viruses, which then adapt to replicate efficiently in their new hosts. However, does replication of aquatic-bird influenza viruses in quail similarly result in their efficient replication in humans? Using sialic acid-galactose linkage-specific lectins, we found both avian (sialic acid-alpha 2-3-galactose [Sia alpha 2-3Gal] linkages on sialyloligosaccharides)- and human (Sia alpha 2-6Gal)-type receptors on the tracheal cells of quail, consistent with previous reports. We also passaged a duck H3N2 virus in quail 19 times. Sequence analysis revealed that eight mutations accumulated in hemagglutinin (HA) during these passages. Interestingly, many of the altered HA amino acids found in the adapted virus are present in human seasonal viruses, but not in duck viruses. We also found that stepwise stalk deletion of neuraminidase occurred during passages, resulting in reduced neuraminidase function. Despite some hemagglutinin mutations near the receptor binding pocket, appreciable changes in receptor specificity were not detected. However, reverse-genetics-generated viruses that possessed the hemagglutinin and neuraminidase of the quail-passaged virus replicated significantly better than the virus possessing the parent HA and neuraminidase in normal human bronchial epithelial cells, whereas no significant difference in replication between the two viruses was observed in duck cells. Further, the quail-passaged but not the original duck virus replicated in human bronchial epithelial cells. These data indicate that quail can serve as intermediate hosts for aquatic-bird influenza viruses to be transmitted to humans.