Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization.

Relative Contribution of Cellular Complement Inhibitors CD59, CD46, and CD55 to Parainfluenza Virus 5 Inhibition of Complement-Mediated Neutralization.
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DOI:
10.3390/v10050219
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发表时间:
2018-04-25
期刊:
Viruses
影响因子:
--
通讯作者:
Parks GD
Parks GD
中科院分区:
其他
文献类型:
--
作者:
Li Y;Parks GD

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补体系统是病毒在感染期间需要面对的先天免疫系统的一部分。许多病毒结合补体激活的细胞调节因子(RCA)来阻断补体途径,我们先前的工作表明副流感病毒5(PIV5)结合CD55和CD46来延迟补体介导的中和。在这篇文章中,我们测试了第三个单独的RCA抑制剂CD59在PIV5与补体途径相互作用中的作用。利用设计表达CD59的细胞系,我们证明了少量的功能性CD59与后代PIV5相关,PIV5能够阻止C5b-C9膜攻击复合体(MAC)的组装。含有CD59的PIV5(PIV5-CD59)在体外对补体介导的中和反应的抵抗力高于缺乏调节剂的PIV5。PIV5和RSV感染A549细胞后CD59表达上调。转化生长因子-β处理的PIV5感染细胞也增加了细胞表面CD59的表达,后代病毒粒子对补体介导的中和更具抵抗力。只含有CD55、CD46或CD59的单个病毒的比较显示出抑制补体介导的中和的效力,这遵循CD55和CD46;CD59的模式。
The complement system is a part of the innate immune system that viruses need to face during infections. Many viruses incorporate cellular regulators of complement activation (RCA) to block complement pathways and our prior work has shown that Parainfluenza virus 5 (PIV5) incorporates CD55 and CD46 to delay complement-mediated neutralization. In this paper, we tested the role of a third individual RCA inhibitor CD59 in PIV5 interactions with complement pathways. Using a cell line engineered to express CD59, we show that small levels of functional CD59 are associated with progeny PIV5, which is capable of blocking assembly of the C5b-C9 membrane attack complex (MAC). PIV5 containing CD59 (PIV5-CD59) showed increased resistance to complement-mediated neutralization in vitro comparing to PIV5 lacking regulators. Infection of A549 cells with PIV5 and RSV upregulated CD59 expression. TGF-beta treatment of PIV5-infected cells also increased cell surface CD59 expression and progeny virions were more resistant to complement-mediated neutralization. A comparison of individual viruses containing only CD55, CD46, or CD59 showed a potency of inhibiting complement-mediated neutralization, which followed a pattern of CD55 > CD46 > CD59.
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