Maturation efficiency of viral glycoproteins in the ER impacts the production of influenza A virus

Maturation efficiency of viral glycoproteins in the ER impacts the production of influenza A virus
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DOI:
10.1016/j.virusres.2008.04.028
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发表时间:
2008-09-01
期刊:
影响因子:
5
通讯作者:
Nakaya, Takaaki
Nakaya, Takaaki
中科院分区:
医学3区
文献类型:
--
作者:
Ueda, Mayo;Yamate, Masanobu;Nakaya, Takaaki

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我们研究了在Madin-Darby犬肾(MDCK)细胞中甲型流感病毒的感染周期中哪些步骤得到增强,MDCK细胞是一种研究用于生产流感疫苗的细胞系,因为其能够产生高水平的病毒。我们已经证实,在感染早期,MDCK在几种细胞系中具有最高的病毒体产生水平。甲型流感病毒在A549中的病毒基因组RNA复制、mRNA转录和蛋白表达水平与MDCK相似。因此,我们集中在翻译后转运病毒糖蛋白从内质网(ER)的质膜。比较表征显示,更有效的处理,在折叠和成熟的血凝素和神经氨酸酶在ER中MDCK比A549。此外,这些糖蛋白随后运输到质膜发生在MDCK早得多。这些结果表明,病毒糖蛋白在ER中的折叠和成熟效率影响产生甲型流感病毒颗粒的效率。(c)2008 Elsevier B. V.保留所有权利。
We have studied which steps are enhanced in the infectious cycle of influenza A virus in Madin-Darby canine kidney (MDCK) cells, a cell line investigated for use in the production of an influenza vaccine because of its ability to yield high levels of virus. We have confirmed that MDCK had the highest production levels of virions among several cell lines early in the infection. Influenza A virus showed similar levels of viral genomic RNA replication, mRNA transcription, and protein expression in A549 as in MDCK. Thus, we focused on the post-translational transport of viral glycoproteins from the endoplasmic reticulum (ER) to the plasma membrane. Comparative characterization revealed more efficient processing in the folding and maturation of hemagglutinin and neuraminidase in the ER in MDCK than in A549. Also, the subsequent transport of these glycoproteins to the plasma membrane occurred much earlier in MDCK. These results indicate that the folding and maturation efficiencies of viral glycoproteins in the ER impact the efficiency with which influenza A viral particles are produced. (c) 2008 Elsevier B.V. All rights reserved.