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

Nectin-1，也称为疱疹病毒进入介体C(HveC)，是一种甲型疱疹病毒受体，通过第一免疫球蛋白(Ig)样结构域与病毒颗粒糖蛋白D(GD)结合。为了比较VCChIg、VpIg和VCCpIg在转基因小鼠中的表达效果，我们建立了三个转基因小鼠系，分别表达由猪Nectin-1的第一个Ig样结构域和猪IgG1的Fc部分组成的融合蛋白(VpIg)或由猪Nectin-1的整个胞外区和猪IgG1的Fc部分组成的融合蛋白(VCCpIg)。用20 LD_(50)、100 LD_(50)和1000 LD_(50)的PRV YS-81株对三种不同的转基因小鼠进行攻击。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VpIg。在10LD_(50)~(GT)的鼻腔攻击中，表达VCChIg和VCCpIg的转基因小鼠与表达VpIg的转基因小鼠相比，总体上表现出较强的保护作用。研究还发现VCChIg和VCCpIg具有几乎相同的抗病毒能力，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的背景下应用于培育抗伪狂犬病的家畜。结果表明，第二和第三类Ig结构域增强了对伪狂犬病病毒感染的抗病毒作用，不同物种的Fc部分对转基因小鼠的抗病毒作用没有明显影响。

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.