Infection of human airway epithelium by human and avian strains of influenza a virus
Infection of human airway epithelium by human and avian strains of influenza a virus
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DOI：
10.1128/jvi.00384-06
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发表时间：
2006-08-01
影响因子：
5.4
通讯作者：
Pickles, Raymond J.
中科院分区：
文献类型：
--
作者：
Thompson, Catherine I.;Barclay, Wendy S.;Pickles, Raymond J.
我们描述了甲型流感病毒感染在体外建立的人假层状粘膜纤毛气道上皮（HAE）模型中的特征。在HAE细胞表面分别检测到人病毒和禽病毒的唾液酸受体α -2,6-和α -2,3-链唾液酸，它们的分布准确地反映了人气管支气管组织的分布。非纤毛细胞具有较高比例的-2,6链唾液酸，而纤毛细胞具有两种唾液酸键。虽然我们发现人类流感病毒在第一轮感染中感染纤毛细胞和非纤毛细胞类型，但最近的人类H3N2病毒在HAE中感染的非纤毛细胞比例高于1968年大流行时期的人类病毒，后者感染的纤毛细胞比例更高。相反，禽流感病毒只感染纤毛细胞。尽管广谱神经氨酸酶能消除人3型副流感病毒对HAE的感染，但这种治疗并没有显著影响流感病毒的感染。所有人类病毒在HAE中都能有效复制，导致感染后6至24小时内从根尖表面释放的新生病毒积累，感染的多重性较低。甲型禽流感病毒也感染HAE，但与人类病毒相比传播有限。最近人类H3N2病毒的非纤毛细胞趋向性反映了对这些细胞类型上显示的唾液酸键的偏好，并表明H3血凝素蛋白在人类中从其禽病毒前体进化而来时，其受体结合表型发生了漂移。
We describe the characterization of influenza A virus infection of an established in vitro model of human pseudostratified mucociliary airway epithelium (HAE). Sialic acid receptors for both human and avian viruses, alpha-2,6- and alpha-2,3-linked sialic acids, respectively, were detected on the HAE cell surface, and their distribution accurately reflected that in human tracheobronchial tissue. Nonciliated cells present a higher proportion of alpha-2,6-linked sialic acid, while ciliated cells possess both sialic acid linkages. Although we found that human influenza viruses infected both ciliated and nonciliated cell types in the first round of infection, recent human H3N2 viruses infected a higher proportion of nonciliated cells in HAE than a 1968 pandemic-era human virus, which infected proportionally more ciliated cells. In contrast, avian influenza viruses exclusively infected ciliated cells. Although a broad-range neuraminidase abolished infection of HAE by human parainfluenza virus type 3, this treatment did not significantly affect infection by influenza viruses. All human viruses replicated efficiently in HAE, leading to accumulation of nascent virus released from the apical surface between 6 and 24 h postinfection with a low multiplicity of infection. Avian influenza A viruses also infected HAE, but spread was limited compared to that of human viruses. The nonciliated cell tropism of recent human H3N2 viruses reflects a preference for the sialic acid linkages displayed on these cell types and suggests a drift in the receptor binding phenotype of the H3 hemagglutinin protein as it evolves in humans away from its avian virus precursor.