GENERATION OF TRANSGENIC MICE EXPRESSING SOLUBLE FORM OF PORCINE NECTIN-1 AS A MODEL FOR PSEUDORABIES-RESISTANT LIVE STOCK

表达可溶形式的猪 NECTIN-1 的转基因小鼠的产生作为抗伪狂犬病家畜的模型

• 批准号: 17580265
• 负责人: ONO Etsuro
• 金额: $ 2.24万
• 依托单位: TOTTORI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17580265/
• 关键词: Disease-resistant animal; Aujeszky's disease; Pseudorabies; Nectin; Transgenic mouse; Herpesvirus

Nectin-1, also known as herpesvirus entry mediator C (HveC), is an alphaherpesvirus receptor that binds to virion glycoprotein D (gD) by the first immunoglobulin (Ig)-like domain. We generated three each transgenic mouse lines expressing a fusion protein (VpIg) consisting of the first Ig-like domain of porcine nectin-1 and the Fc portion of porcine IgG1 or a fusion protein (VCCpIg) consisting of the entire ectodomain of porcine nectin-1 and the Fc portion of porcine IgG1 to compare the protective effects induced by the expression of VCChIg, VpIg and VCCpIg in the transgenic mice. Three different transgenic mouse lines were challenged with 20 LD_<50>, 100 LD_50 or 1000 LD_<50> of PRV strainYS-81 via intraperitoneal route. In the higher virus doses, significantly stronger protections were induced by the expression of VCChIg and VCCpIg as compared with those by VpIg. In the intranasal challenge with 10 LD_<50> of PRV, relatively strong protection was, taken overall, observed in the transgenic mouse lines expressing VCChIg and VCCpIg as compared with that in the lines expressing VpIg. It was also found that both of VCChIg and VCCpIg possess the almost same antiviral potential, indicating that the VCCpIg gene may be more suitable for the application for generating pseudorabies-resistant livestock in the context of porcine immune system and the issue of possible adverse effects. The present results demonstrate that the second and third Ig-like domains enhance the antiviral effect against pseudorabies virus infection and the Fc portions from different species do not significantly affect the antiviral potential in transgenic mice.

Nectin-1，也称为疱疹病毒进入介体C（HveC），是α疱疹病毒受体，其通过第一免疫球蛋白（IG）样结构域与病毒体糖蛋白D（gD）结合。我们分别建立了三个转基因小鼠品系，它们表达由猪nectin-1的第一Ig样结构域和猪IgG 1的Fc部分组成的融合蛋白（VpIg）或由猪nectin-1的整个胞外结构域和猪IgG 1的Fc部分组成的融合蛋白（VCCpIg），以比较在转基因小鼠中表达VCChIg、VpIg和VCCpIg诱导的保护作用。用20 LD_（50）<50>、100 LD_（50）或1000 LD_<50>（50）的PRV YS-81株经腹腔途径攻击三种不同的转基因小鼠品系。在较高的病毒剂量下，与VpIg相比，VCChIg和VCCpIg的表达诱导的保护作用显著增强。在10 LD的PRV鼻内攻击中<50>，与表达VpIg的转基因小鼠相比，表达VCChIg和VCCpIg的转基因小鼠总体上观察到相对较强的保护作用。同时发现VCChIg和VCCpIg具有几乎相同的抗病毒潜力，表明VCCpIg基因可能更适合于在猪免疫系统和可能的不良反应问题的背景下应用于产生伪狂犬病抗性家畜。目前的结果表明，第二和第三Ig样结构域增强了抗伪狂犬病病毒感染的抗病毒作用，并且来自不同物种的Fc部分在转基因小鼠中不显著影响抗病毒潜力。

项目成果

Comparison of protection levels against pseudorabies virus infection of transgenic mice expressing a soluble form of porcine nectin-1/HveC and vaccinated mice

• DOI: 10.1016/j.vetmic.2005.12.011
• 发表时间: 2006-05-31
• 期刊: VETERINARY MICROBIOLOGY
• 影响因子: 3.3
• 作者: Ono, Etsuro;Tomioka, Yukiko;Cherel, Pierre
• 通讯作者: Cherel, Pierre

The first immunoglobulin-like domain of porcine nectin-1 is sufficient to confer resistance to pseudorabies virus infection in transgenic mice

• DOI: 10.1007/s00705-006-0747-6
• 发表时间: 2006-04
• 期刊: Archives of Virology
• 影响因子: 2.7
• 作者: E. Ono;Y. Tomioka;Y. Watanabe;K. Amagai;S. Taharaguchi;J. Glénisson;P. Chérel