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

The first immunoglobulin-like domain of porcine nectin-1 is sufficient to confer resistance to pseudorabies virus infection in transgenic mice
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DOI:
10.1007/s00705-006-0747-6
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发表时间:
2006-04
影响因子:
2.7
通讯作者:
E. Ono;Y. Tomioka;Y. Watanabe;K. Amagai;S. Taharaguchi;J. Glénisson;P. Chérel
E. Ono;Y. Tomioka;Y. Watanabe;K. Amagai;S. Taharaguchi;J. Glénisson;P. Chérel
中科院分区:
医学4区
文献类型:
--
作者:
E. Ono;Y. Tomioka;Y. Watanabe;K. Amagai;S. Taharaguchi;J. Glénisson;P. Chérel

文献摘要

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Nectin-1是一种结合病毒粒子糖蛋白D (gD)的α疱疹病毒受体。猪连接素-1介导假狂犬病毒(PRV)、单纯疱疹病毒1型和2型(HSV-1和HSV-2)和牛疱疹病毒1型(BHV-1)的进入。连接蛋白-1的gd结合域是整个外结构域的第一个或n端免疫球蛋白(Ig)样结构域。在这里,我们产生了三个转基因小鼠系,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,以评估nectin-1的第一个igg样结构域在体内的抗病毒潜力。所有转基因小鼠系通过腹腔接种对PRV感染表现出显著的抗性(存活率为67% ~ 100%)。在鼻内攻击中,观察到较低但仍然显著的保护;三种转基因小鼠的存活率为21%至55%。目前的研究结果表明,猪连接素-1第一结构域的可溶性形式能够对伪狂犬病毒感染发挥显著的抗病毒作用。
Nectin-1 is an alphaherpesvirus receptor that binds to virion glycoprotein D (gD). Porcine nectin-1 mediates entry of pseudorabies virus (PRV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), and bovine herpesvirus type 1 (BHV-1). The gD-binding domain of nectin-1 is the first or N-terminal immunoglobulin (Ig)-like domain of the entire ectodomain. Here, we generated three transgenic mouse lines expressing a fusion protein consisting of the first Ig-like domain of porcine nectin-1 and the Fc portion of porcine IgG1 to assess the antiviral potential of the first Ig-like domain of nectin-1in vivo. All of the transgenic mouse lines showed significant resistance to PRV infection via intraperitoneal inoculation (survival rates of 67% to 100%). In the intranasal challenge, a lower but still significant protection was observed; 21% to 55% of the animals from the three transgenic mouse lines survived. The present results demonstrate that a soluble form of the first domain of porcine nectin-1 is able to exert a significant antiviral effect against pseudorabies virus infection.