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

Nectin-1，也被称为疱疹病毒进入介质C (HveC)，是一种通过第一免疫球蛋白（Ig）样结构域与病毒粒子糖蛋白D （gD）结合的α疱疹病毒受体。我们分别构建了3个转基因小鼠系，分别表达由猪nectin-1的第一个igg样结构域和猪IgG1的Fc部分组成的融合蛋白（VpIg）或由猪nectin-1的整个外结构域和猪IgG1的Fc部分组成的融合蛋白（VCCpIg），比较表达VCChIg、VpIg和VCCpIg对转基因小鼠的保护作用。分别以20株LD_<50>、100株LD_50和1000株LD_<50>的PRV菌株ys -81进行腹腔注射。在较高的病毒剂量下，VCChIg和VCCpIg的表达诱导的保护作用明显强于VCCpIg。在10 LD_<50> PRV的鼻内攻击中，表达VCChIg和VCCpIg的转基因小鼠系与表达VpIg的小鼠系相比，总体上具有较强的保护作用。研究还发现，VCChIg和VCCpIg具有几乎相同的抗病毒潜力，这表明在猪免疫系统和可能的不良反应问题的背景下，VCCpIg基因可能更适合用于产生伪狂犬病抗性家畜。本研究结果表明，第二和第三个igg样结构域增强了对伪狂犬病毒感染的抗病毒作用，而来自不同物种的Fc部分对转基因小鼠的抗病毒潜力没有显著影响。

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.