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基于日本脑炎活疫苗株SA14-14-2的嵌合鸭坦布苏病毒的体外和体内特性研究

In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2.

作者信息

Wang Hong-Jiang, Liu Long, Li Xiao-Feng, Ye Qing, Deng Yong-Qiang, Qin E-De, Qin Cheng-Feng

机构信息

Department of Virology, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing 100071, PR China.

Graduate School, Anhui Medical University, Hefei 230032, PR China.

出版信息

J Gen Virol. 2016 Jul;97(7):1551-1556. doi: 10.1099/jgv.0.000486. Epub 2016 Apr 21.

Abstract

Duck Tembusu virus (DTMUV), a newly identified flavivirus, has rapidly spread to China, Malaysia and Thailand. The potential threats to public health have been well-highlighted; however its virulence and pathogenesis remain largely unknown. Here, by using reverse genetics, a recombinant chimeric DTMUV based on Japanese encephalitis live vaccine strain SA14-14-2 was obtained by substituting the corresponding prM and E genes (named ChinDTMUV). In vitro characterization demonstrated that ChinDTMUV replicated efficiently in mammalian cells with small-plaque phenotype in comparison with its parental viruses. Mouse tests showed ChinDTMUV exhibited avirulent phenotype in terms of neuroinvasiveness, while it retained neurovirulence from its parental virus DTMUV. Furthermore, immunization with ChinDTMUV was evidenced to elicit robust IgG and neutralizing antibody responses in mice. Overall, we successfully developed a viable chimeric DTMUV, and these results provide a useful platform for further investigation of the pathogenesis of DTMUV and development of a live attenuated DTMUV vaccine candidate.

摘要

鸭坦布苏病毒(DTMUV)是一种新发现的黄病毒,已迅速传播至中国、马来西亚和泰国。其对公众健康的潜在威胁已得到充分凸显;然而,其毒力和发病机制仍 largely 未知。在此,通过反向遗传学,基于日本脑炎活疫苗株 SA14 - 14 - 2,通过替换相应的 prM 和 E 基因获得了一种重组嵌合 DTMUV(命名为 ChinDTMUV)。体外特性表明,与亲本病毒相比,ChinDTMUV 在哺乳动物细胞中高效复制,具有小斑块表型。小鼠试验表明,ChinDTMUV 在神经侵袭方面表现出无毒力表型,而它保留了亲本病毒 DTMUV 的神经毒力。此外,用 ChinDTMUV 免疫证明在小鼠中引发了强烈的 IgG 和中和抗体反应。总体而言,我们成功开发了一种可行的嵌合 DTMUV,这些结果为进一步研究 DTMUV 的发病机制和开发减毒活 DTMUV 疫苗候选物提供了一个有用的平台。

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