Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells

Efficient influenza B virus propagation due to deficient interferon-induced antiviral activity in MDCK cells
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DOI:
10.1016/j.vaccine.2011.05.069
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发表时间:
2011-09-22
期刊:
影响因子:
5.5
通讯作者:
Reichl, Udo
Reichl, Udo
中科院分区:
医学3区
文献类型:
--
作者:
Frensing, Timo;Seitz, Claudius;Reichl, Udo

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B型流感病毒感染主要局限于人类,这部分是由于B型流感病毒NS 1蛋白无法抵消其他物种的先天免疫反应所致。然而,对于基于细胞培养的流感疫苗生产,通常使用非人细胞,例如Madin-Darby犬肾(MDCK)细胞。因此,本研究分析了细胞病原体防御机制对MDCK细胞中流感B病毒繁殖的影响。通过干扰素刺激激活细胞抗病毒防御在早期时间点减缓了流感B病毒复制,但在48小时后,在刺激细胞和对照细胞中达到相同的病毒滴度。此外,抑制抗病毒宿主防御的病毒拮抗剂,狂犬病病毒磷蛋白的瞬时表达,不能增加流感B病毒复制。最后,犬粘病毒抗性(Mx)蛋白在流感B病毒特异性微复制子测定中显示出与鼠Mx 1蛋白相反的抗病毒活性。总之,这些结果表明,MDCK细胞中抗病毒防御不足促进了有效的B型流感病毒复制,有利于在流感疫苗生产中使用MDCK细胞。(C)2011爱思唯尔有限公司版权所有。
Influenza B virus infections are mainly restricted to humans, which is partially caused by the inability of influenza B virus NS1 protein to counteract the innate immune response of other species. However, for cell culture-based influenza vaccine production non-human cells, such as Madin-Darby canine kidney (MDCK) cells, are commonly used. Therefore, the impact of cellular pathogen defence mechanisms on influenza B virus propagation in MDCK cells was analysed in this study. Activation of the cellular antiviral defence by interferon stimulation slowed down influenza B virus replication at early time points but after 48 h the same virus titres were reached in stimulated and control cells. Furthermore, suppression of the antiviral host defence by transient expression of a viral antagonist, the rabies virus phosphoprotein, could not increase influenza B virus replication. Finally, canine Myxovirus resistance (Mx) proteins showed no antiviral activity in an influenza B virus-specific minireplicon assay in contrast to the murine Mx1 protein. Taken together, these results indicate that an insufficient antiviral defence in MDCK cells promotes efficient influenza B virus replication favouring the use of MDCK cells in influenza vaccine production. (C) 2011 Elsevier Ltd. All rights reserved.