Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells.
Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells.
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DOI：
10.1038/s41598-017-10749-5
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发表时间：
2017-09-12
影响因子：
4.6
通讯作者：
Huang LM
中科院分区：
文献类型：
--
作者：
Huang DT;Lu CY;Chi YH;Li WL;Chang LY;Lai MJ;Chen JS;Hsu WM;Huang LM
甲型H7N9流感是一种新出现的具有大流行潜力的人畜共患病原体。为了了解其适应能力，我们研究了A（H7N9）在原代人气道上皮细胞（hAEC）中连续感染后的遗传变化和细胞反应。连续传代35代后，发现6个氨基酸突变，即HA（R54 G，T160 A，Q226 L，H3编号），NA（K289 R，或N2编号的K292 R），NP（V363 V/I）和PB 2（L/R332 R）。HA中的突变使A（H7N9）病毒能够以更高的亲和力（从39.2%至53.4%）与唾液酸α 2，6-半乳糖（SAα 2，6-Gal）连接的受体结合。hAEC中促炎细胞因子的产生在较晚的传代中被引发，并且在感染后24小时IL-6、MIP-1α和MCP-1水平的较早峰值。hAEC中的病毒复制能力在整个35代中保持在相似的水平。总之，在甲型流感（H7N9）病毒连续感染hAEC期间，注意到病毒粒子与细胞受体的结合增强，随后出现更强的先天性细胞应答，但未观察到病毒复制增强。这表明甲型H7N9流感病毒在人与人之间有效传播存在可能的进化障碍。
Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs). After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39.2% to 53.4%) to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. A greater production of proinflammatory cytokines in hAECs was elicited at later passages together with earlier peaking at 24 hours post infection of IL-6, MIP-1α, and MCP-1 levels. Viral replication capacity in hAECs maintained at similar levels throughout the 35 passages. In conclusion, during the serial infections of hAECs by influenza A(H7N9) virus, enhanced binding of virion to cell receptors with subsequent stronger innate cell response were noted, but no enhancement of viral replication could be observed. This indicates the existence of possible evolutional hurdle for influenza A(H7N9) virus to transmit efficiently from human to human.
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影响因子：
5.4
作者：
Ioannidis, Ioannis;McNally, Beth;Flano, Emilio
通讯作者：
Flano, Emilio
人类感染新型禽源甲型流感 (H7N9) 病毒。
影响因子：
158.5
作者：
Gao, Rongbao;Cao, Bin;Shu, Yuelong
通讯作者：
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影响因子：
64.8
作者：
Lam, Tommy Tsan-Yuk;Zhou, Boping;Zhu, Huachen
通讯作者：
Zhu, Huachen
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
DOI：
10.1126/science.1213362
发表时间：
2012-06-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Herfst S;Schrauwen EJ;Linster M;Chutinimitkul S;de Wit E;Munster VJ;Sorrell EM;Bestebroer TM;Burke DF;Smith DJ;Rimmelzwaan GF;Osterhaus AD;Fouchier RA
通讯作者：
Fouchier RA