Serotype-specific anti-Dengue virus NS1 mouse antibodies cross-react with prM and are potentially involved in virus production.

Serotype-specific anti-Dengue virus NS1 mouse antibodies cross-react with prM and are potentially involved in virus production.
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DOI:
10.1089/vim.2012.0102
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发表时间:
2013-08
期刊:
影响因子:
2.2
通讯作者:
P. Masrinoul;M. D. Omokoko;S. Pambudi;K. Ikuta;T. Kurosu
P. Masrinoul;M. D. Omokoko;S. Pambudi;K. Ikuta;T. Kurosu
中科院分区:
医学4区
文献类型:
--
作者:
P. Masrinoul;M. D. Omokoko;S. Pambudi;K. Ikuta;T. Kurosu

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登革病毒(DENV)感染诱导针对病毒非结构蛋白1(NS 1)的强烈B细胞免疫应答。抗NS 1抗体(Abs)可能会影响病毒的产生,因为它们与患者血液中的病毒共存。本研究检查了针对NS 1产生的10种小鼠单克隆抗体(MAbs)是否影响DENV-2的产生。三种单克隆抗体4C 2、4G 11和4 E5在病灶减少测定中显示弱中和活性。此外,两种DENV-2型特异性单克隆抗体4C 2和4G 11可保护乳鼠免受DENV-2的致死性感染。用DENV-2的免疫沉淀测定显示,这些对DENV-4和DENV-1的NS 1具有特异性的MAbs与DENV-2前膜(prM)蛋白交叉反应,但不与DENV-2 NS 1交叉反应。有趣的是,高浓度的MAb 4G 11在人单核细胞THP-1细胞中显示出DENV-2感染的抗体依赖性增强。综上所述,这些观察结果表明,病毒型特异性抗NS 1单克隆抗体可能参与病毒的产生。
Dengue virus (DENV) infection induces a strong B-cell immune response against the viral nonstructural protein 1 (NS1). Anti-NS1 antibodies (Abs) may affect virus production because they coexist with the virus in the patients' blood. The present study examined whether ten mouse monoclonal antibodies (MAbs) raised against NS1 affected production of the DENV-2. Three MAbs, 4C2, 4G11, and 4E5, showed weak neutralizing activity in a focus reduction assay. In addition, two serotype-specific MAbs, 4C2 and 4G11, protected suckling mice from lethal infection with DENV-2. An immunoprecipitation assay with DENV-2 showed that these MAbs, which were specific for the NS1 of DENV-4 and DENV-1, cross-reacted with the DENV-2 pre-membrane (prM) protein, but not with DENV-2 NS1. Interestingly, high concentrations of MAb 4G11 showed antibody-dependent enhancement of DENV-2 infection in human monocyte THP-1 cells. Taken together, these observations suggest that serotype-specific anti-NS1 MAbs are potentially involved in virus production.