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通过基于 NS1 的捕获 ELISA 发现,在自然发生的人类 ZIKV 感染期间,针对非结构蛋白 1(NS1)的延迟和高度特异性抗体反应。

Delayed and highly specific antibody response to nonstructural protein 1 (NS1) revealed during natural human ZIKV infection by NS1-based capture ELISA.

机构信息

Guangzhou Eighth People's Hospital, Guangzhou Medical University, 627 Dongfeng Rd. East, Guangzhou, 510060, China.

Viral Disease and Vaccine Translational Research Unit, CAS Key Lab of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences (CAS), Shanghai, 200025, China.

出版信息

BMC Infect Dis. 2018 Jun 14;18(1):275. doi: 10.1186/s12879-018-3173-y.

DOI:10.1186/s12879-018-3173-y
PMID:29898684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6000977/
Abstract

BACKGROUND

Zika virus (ZIKV) had spread rapidly in the past few years in southern hemisphere where dengue virus (DENV) had caused epidemic problems for over half a century. The high degree of cross-reactivity of Envelope (E) protein specific antibody responses between ZIKV and DENV made it challenging to perform differential diagnosis between the two infections using standard ELISA method for E protein.

METHODS

Using an IgG capture ELISA, we investigated the kinetics of nonstructural protein 1 (NS1) antibody response during natural ZIKV infection and the cross-reactivity to NS1 proteins using convalescent sera obtained from patients infected by either DENV or ZIKV.

RESULTS

The analyses of the sequential serum samples from ZIKV infected individuals showed NS1 specific Abs appeared 2 weeks later than E specific Abs. Notably, human sera from ZIKV infected individuals did not contain cross-reactivity to NS1 proteins of any of the four DENV serotypes. Furthermore, four out of five NS1-specific monoclonal antibodies (mAbs) isolated from ZIKV infected individuals did not bind to DENV NS1 proteins. Only limited amount of cross-reactivity to ZIKV NS1 was displayed in 108 DENV1 immune sera at 1:100 dilution.

CONCLUSIONS

The high degree of NS1-specific Abs in both ZIKV and DENV infection revealed here suggest that NS1-based diagnostics would significantly improve the differential diagnosis between DENV and ZIKV infections.

摘要

背景

寨卡病毒(ZIKV)在过去几年中在南半球迅速传播,而登革热病毒(DENV)已经在那里造成了半个多世纪的流行问题。E 蛋白特异性抗体反应之间的高度交叉反应性,使得使用 E 蛋白的标准 ELISA 方法对这两种感染进行鉴别诊断具有挑战性。

方法

我们使用 IgG 捕获 ELISA 法,研究了自然 ZIKV 感染期间非结构蛋白 1(NS1)抗体反应的动力学,以及使用从感染 DENV 或 ZIKV 的患者获得的恢复期血清对 NS1 蛋白的交叉反应性。

结果

对 ZIKV 感染个体的连续血清样本的分析表明,NS1 特异性 Abs 比 E 特异性 Abs 晚出现 2 周。值得注意的是,来自 ZIKV 感染个体的人血清不含有对任何四种 DENV 血清型的 NS1 蛋白的交叉反应性。此外,从 ZIKV 感染个体中分离出的五种 NS1 特异性单克隆抗体(mAb)中有四种不与 DENV NS1 蛋白结合。在 1:100 稀释度下,仅在 108 份 DENV1 免疫血清中显示出对 ZIKV NS1 的有限量的交叉反应性。

结论

在此处揭示的 ZIKV 和 DENV 感染中高度的 NS1 特异性 Abs 表明,基于 NS1 的诊断方法将显著改善 DENV 和 ZIKV 感染之间的鉴别诊断。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/37cc390560e0/12879_2018_3173_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/490bf2ee2e47/12879_2018_3173_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/efc23e2573f6/12879_2018_3173_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/2da87a29bc14/12879_2018_3173_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/37cc390560e0/12879_2018_3173_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/490bf2ee2e47/12879_2018_3173_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/efc23e2573f6/12879_2018_3173_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/2da87a29bc14/12879_2018_3173_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4746/6000977/37cc390560e0/12879_2018_3173_Fig4_HTML.jpg

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