NA proteins of influenza A viruses H1N1/2009, H5N1, and H9N2 show differential effects on infection initiation, virus release, and cell-cell fusion.
NA proteins of influenza A viruses H1N1/2009, H5N1, and H9N2 show differential effects on infection initiation, virus release, and cell-cell fusion.
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甲型流感病毒 H1N1/2009、H5N1 和 H9N2 的 NA 蛋白对感染起始、病毒释放和细胞融合有不同的影响
DOI：
10.1371/journal.pone.0054334
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Chen Q;Huang S;Chen J;Zhang S;Chen Z
流感病毒的两种表面糖蛋白，血凝素（HA）和神经氨酸酶（NA），在与宿主唾液酸受体的相互作用方面发挥相反的作用。 HA 附着在宿主细胞表面受体上的唾液酸上以引发病毒感染，而 NA 则去除这些唾液酸以促进子代病毒颗粒的释放。这种功能上的对立需要平衡。为了探讨当流感病毒的 NA 被另一种分离株或亚型的 NA 取代时会发生什么，在本研究中，我们以 A/PR/8/34 (PR8) (H1N1) 为背景，使用分别从 2009 年大流行的 H1N1 病毒、一种高致病性禽类 H5N1 病毒和一种低致病性禽类获得的 NA 基因，生成了三种重组甲型流感病毒。 H9N2 病毒。这些重组病毒 rPR8-H1N1NA、rPR8-H5N1NA 和 rPR8-H9N2NA 在细胞中具有相似的生长动力学，在小鼠中具有相似的致病性。然而，1小时后，鸡红细胞释放的rPR8-H5N1NA和PR8-wt病毒体比rPR8-H1N1NA和rPR8-H9N2NA病毒体多得多。此外，在MDCK细胞中，rPR8-H5N1NA和rPR8-H9N2NA在感染早期感染了更高比例的细胞，并且比PR8-wt和rPR8-H1N1NA更快、更广泛地诱导细胞-细胞融合。总之，本研究中的NA替换并不影响病毒复制动力学，但对感染起始、病毒释放和感染细胞融合有不同的影响。这些现象可能部分归因于 NA 蛋白对 α2-3/2-6-唾液酸化碳水化合物链的不同特异性，但确切的机制仍有待探索。
Two surface glycoproteins of influenza virus, haemagglutinin (HA) and neuraminidase (NA), play opposite roles in terms of their interaction with host sialic acid receptors. HA attaches to sialic acid on host cell surface receptors to initiate virus infection while NA removes these sialic acids to facilitate release of progeny virions. This functional opposition requires a balance. To explore what might happen when NA of an influenza virus was replaced by one from another isolate or subtype, in this study, we generated three recombinant influenza A viruses in the background of A/PR/8/34 (PR8) (H1N1) and with NA genes obtained respectively from the 2009 pandemic H1N1 virus, a highly pathogenic avian H5N1 virus, and a lowly pathogenic avian H9N2 virus. These recombinant viruses, rPR8-H1N1NA, rPR8-H5N1NA, and rPR8-H9N2NA, were shown to have similar growth kinetics in cells and pathogenicity in mice. However, much more rPR8-H5N1NA and PR8-wt virions were released from chicken erythrocytes than virions of rPR8-H1N1NA and rPR8-H9N2NA after 1 h. In addition, in MDCK cells, rPR8-H5N1NA and rPR8-H9N2NA infected a higher percentage of cells, and induced cell-cell fusion faster and more extensively than PR8-wt and rPR8-H1N1NA did in the early phase of infection. In conclusion, NA replacement in this study did not affect virus replication kinetics but had different effects on infection initiation, virus release and fusion of infected cells. These phenomena might be partially due to NA proteins’ different specificity to α2-3/2-6-sialylated carbohydrate chains, but the exact mechanism remains to be explored.
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影响因子：
3.8
作者：
Chen, Jingjing;Huang, Shengping;Chen, Ze
通讯作者：
Chen, Ze
DOI：
10.1073/pnas.0405172102
发表时间：
2004-12-28
影响因子：
11.1
作者：
Chu, VC;Whittaker, GR
通讯作者：
Whittaker, GR
影响因子：
6.4
作者：
Morens, David M.;Fauci, Anthony S.
通讯作者：
Fauci, Anthony S.
影响因子：
5.4
作者：
Huang, I-Chueh;Li, Wenhui;Farzan, Michael
通讯作者：
Farzan, Michael
影响因子：
5.8
作者：
Ohuchi, Masanobu;Asaoka, Naoko;Ohuchi, Reiko
通讯作者：
Ohuchi, Reiko