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基于 DNA 的西尼罗河病毒复制子在小鼠中引发体液和细胞免疫应答。

A DNA-based West Nile virus replicon elicits humoral and cellular immune responses in mice.

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Epidemiology and Microbiology, 20 Dongda Street, Fengtai District, Beijing 100071, China.

出版信息

J Virol Methods. 2011 Dec;178(1-2):87-93. doi: 10.1016/j.jviromet.2011.08.018. Epub 2011 Aug 24.

Abstract

While self-replicating, non-infectious subgenomic flavivirus replicons have been described, most of them are RNA transcripts under the control of an Sp6 or T7 promoter. In this study, using West Nile virus (WNV) as a model, a series of DNA-based reporter replicons under the control of a minimal cytomegalovirus (CMV) immediate-early promoter were constructed, and functional analysis showed that these reporter replicons replicate efficiently in mammalian cells. When the DNA-based WNV replicon was used to immunize mice, NS1-specific IgG antibodies and anti-WNV neutralizing antibodies were both induced. Additionally, immunization with this DNA-based WNV replicon induced high levels of lymphocyte proliferation and enhanced the secretion of IFN-γ. These results suggest that this type of DNA-based replicon can induce humoral and cellular immune responses in mice, indicating that this type of DNA-based replicon may serve as a useful platform for vaccine development and protein expression.

摘要

虽然已经描述了自我复制、非感染性亚基因组黄病毒复制子,但它们大多数是在 Sp6 或 T7 启动子控制下的 RNA 转录本。在这项研究中,我们使用西尼罗河病毒 (WNV) 作为模型,构建了一系列受最小巨细胞病毒 (CMV) 早期启动子控制的基于 DNA 的报告复制子,功能分析表明这些报告复制子在哺乳动物细胞中能够高效复制。当使用基于 DNA 的 WNV 复制子对小鼠进行免疫接种时,诱导产生了 NS1 特异性 IgG 抗体和抗 WNV 中和抗体。此外,用这种基于 DNA 的 WNV 复制子进行免疫接种可诱导高水平的淋巴细胞增殖,并增强 IFN-γ 的分泌。这些结果表明,这种类型的基于 DNA 的复制子可以在小鼠中诱导体液和细胞免疫应答,表明这种类型的基于 DNA 的复制子可能作为疫苗开发和蛋白表达的有用平台。

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