Expression of SARS coronavirus 1 spike protein from a herpesviral vector induces innate immune signaling and neutralizing antibody responses.

Expression of SARS coronavirus 1 spike protein from a herpesviral vector induces innate immune signaling and neutralizing antibody responses.
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DOI:
10.1016/j.virol.2021.04.006
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发表时间:
2021-07
期刊:
影响因子:
3.7
通讯作者:
Knipe DM
Knipe DM
中科院分区:
医学3区
文献类型:
--
作者:
Kurt-Jones EA;Dudek TE;Watanabe D;Mandell L;Che J;Zhou S;Cao L;Greenough T;Babcock GJ;Diaz F;Oh HS;Zhou C;Finberg RW;Knipe DM

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SARS冠状病毒1(SARS-CoV-1)可引起呼吸道感染,可导致急性呼吸窘迫,其特征是肺部组织中炎症和高水平的细胞因子。在本研究中,我们构建了表达SARS-CoV-1刺突蛋白的单纯疱疹病毒1型复制缺陷突变载体,作为潜在的疫苗载体,并探讨了刺突蛋白对宿主细胞的影响。该载体表达的Spike蛋白定位于感染细胞表面,并诱导表达ACE2的细胞融合,具有一定的功能。在免疫的小鼠中,重组载体诱导的抗体在酶联免疫吸附试验中与Spike蛋白结合,并显示中和活性。该载体表达的Spike蛋白可诱导ACE2非依赖、MyD88依赖的细胞因子的表达。这些结果表明,SARS-CoV-1刺突蛋白本质上激活了诱导细胞因子的信号通路,并直接参与了SARS的炎症过程。
SARS coronavirus 1 (SARS-CoV-1) causes a respiratory infection that can lead to acute respiratory distress characterized by inflammation and high levels of cytokines in the lung tissue. In this study we constructed a herpes simplex virus 1 replication-defective mutant vector expressing SARS-CoV-1 spike protein as a potential vaccine vector and to probe the effects of spike protein on host cells. The spike protein expressed from this vector is functional in that it localizes to the surface of infected cells and induces fusion of ACE2-expressing cells. In immunized mice, the recombinant vector induced antibodies that bind to spike protein in an ELISA assay and that show neutralizing activity. The spike protein expressed from this vector can induce the expression of cytokines in an ACE2-independent, MyD88-dependent process. These results argue that the SARS-CoV-1 spike protein intrinsically activates signaling pathways that induce cytokines and contribute directly to the inflammatory process of SARS.
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