Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins.
Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins.
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抗体依赖性SARS冠状病毒感染是由针对峰值蛋白的抗体介导的。
DOI：
10.1016/j.bbrc.2014.07.090
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发表时间：
2014-08-22
影响因子：
3.1
通讯作者：
Huang JC
中科院分区：
文献类型：
--
作者：
Wang SF;Tseng SP;Yen CH;Yang JY;Tsao CH;Shen CW;Chen KH;Liu FT;Liu WT;Chen YM;Huang JC
SARS冠状病毒表现出抗体依赖性增强（ADE）。SARS-CoV ADE由抗刺突抗体而非抗核衣壳抗体强烈介导。以前未经测试的HL-CZ细胞对SARS-CoV感染敏感。高度稀释的SARS-CoV抗血清增强了SARS-CoV的感染性。严重急性呼吸道综合征冠状病毒（SARS-CoV）仍然具有重新出现的可能性，因此正在努力开发疫苗作为控制和预防的预防性策略。抗体依赖性增强（ADE）是登革热病毒、猫冠状病毒和HIV病毒利用抗病毒体液免疫应答感染宿主靶细胞的机制。在这里，我们描述了我们的观察SARS-CoV使用ADE，以提高HL-CZ人前单核细胞系的感染性。定量PCR和免疫荧光染色结果表明，SARS-CoV能够在HL-CZ细胞中复制，并在感染后2天表现出病毒诱导的细胞病变效应和TNF-α、IL-4和IL-6水平的升高。根据流式细胞术数据，HL-CZ细胞还表达血管紧张素转换酶2（ACE 2，SARS-CoV受体）和更高水平的FcγRII受体。我们发现，较高浓度的抗SARS-CoV血清中和SARS-CoV感染，而高度稀释的抗血清显着增加SARS-CoV感染，并诱导更高水平的细胞凋亡。感染性试验的结果表明，SARS-CoV ADE主要是由稀释的抗包膜刺突蛋白抗体介导的，而不是核衣壳蛋白。我们还产生了针对SARS-CoV刺突蛋白的单克隆抗体，并观察到它们中的大多数促进SARS-CoV感染。结合，我们的研究结果表明，针对SARS-CoV刺突蛋白的抗体可能会触发ADE效应。这些数据提出了关于潜在的SARS-CoV疫苗的新问题，同时阐明了SARS发病机制。
The SARS coronavirus exhibits antibody-dependent enhancement (ADE). SARS-CoV ADE is strongly mediated by anti-spike but not anti-nucleocapsid Abs. Formerly untested HL-CZ cells are susceptible to SARS-CoV infection. Highly diluted anti-sera against SARS-CoV enhances SARS-CoV infectivity. The severe acute respiratory syndrome coronavirus (SARS-CoV) still carries the potential for reemergence, therefore efforts are being made to create a vaccine as a prophylactic strategy for control and prevention. Antibody-dependent enhancement (ADE) is a mechanism through which dengue viruses, feline coronaviruses, and HIV viruses take advantage of anti-viral humoral immune responses to infect host target cells. Here we describe our observations of SARS-CoV using ADE to enhance the infectivity of a HL-CZ human promonocyte cell line. Quantitative-PCR and immunofluorescence staining results indicate that SARS-CoV is capable of replication in HL-CZ cells, and of displaying virus-induced cytopathic effects and increased levels of TNF-α, IL-4 and IL-6 two days post-infection. According to flow cytometry data, the HL-CZ cells also expressed angiotensin converting enzyme 2 (ACE2, a SARS-CoV receptor) and higher levels of the FcγRII receptor. We found that higher concentrations of anti-sera against SARS-CoV neutralized SARS-CoV infection, while highly diluted anti-sera significantly increased SARS-CoV infection and induced higher levels of apoptosis. Results from infectivity assays indicate that SARS-CoV ADE is primarily mediated by diluted antibodies against envelope spike proteins rather than nucleocapsid proteins. We also generated monoclonal antibodies against SARS-CoV spike proteins and observed that most of them promoted SARS-CoV infection. Combined, our results suggest that antibodies against SARS-CoV spike proteins may trigger ADE effects. The data raise new questions regarding a potential SARS-CoV vaccine, while shedding light on mechanisms involved in SARS pathogenesis.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
9.4
作者：
Chen, YMA;Liang, SY;Chu, DC
通讯作者：
Chu, DC
影响因子：
5.4
作者：
Jaume, Martial;Yip, Ming S.;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik
影响因子：
5.4
作者：
Barnett, Susan W.;Burke, Brian;Srivastava, Indresh K.
通讯作者：
Srivastava, Indresh K.
影响因子：
5.4
作者：
Shih, Yi-Ping;Chen, Chia-Yen;Chen, Yi-Ming Arthur
通讯作者：
Chen, Yi-Ming Arthur