Fusion protein consisting of the first immunoglobulin‐like domain of porcine nectin‐1 and Fc portion of human IgG1 provides a marked resistance against pseudorabies virus infection to transgenic mice

Fusion protein consisting of the first immunoglobulin‐like domain of porcine nectin‐1 and Fc portion of human IgG1 provides a marked resistance against pseudorabies virus infection to transgenic mice
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由猪nectin-1的第一个免疫球蛋白样结构域和人IgG1的Fc部分组成的融合蛋白为转基因小鼠提供了对伪狂犬病病毒感染的显着抵抗力

DOI:
10.1111/j.1348-0421.2008.00082.x
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发表时间:
2009
影响因子:
2.6
通讯作者:
E. Ono
E. Ono
中科院分区:
医学4区
文献类型:
--
作者:
Y. Tomioka;M. Morimatsu;K. Amagai;Minako Kuramochi;Yuki Watanabe;Shigeto Kouda;T. Wada;Noritaka Kuboki;E. Ono

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Nectin-1 是一种不依赖 Ca2+ 的 Ig 样细胞间粘附分子,也是一种 α-疱疹病毒受体,通过第一个 Ig 样结构域与病毒体糖蛋白 D 结合。我们通过产生表达不同类型融合蛋白的转基因小鼠,研究了可溶形式的猪nectin-1对PRV感染的抗病毒潜力。此前,我们报道过,携带与猪 IgG1 Fc 部分融合的猪 nectin-1 整个胞外域的嵌合体转基因小鼠比携带与 Fc 部分融合的第一个 Ig 样结构域的嵌合体转基因小鼠具有更强的抵抗力。最近,我们培育了表达融合蛋白的转基因小鼠,该融合蛋白由第一个 Ig 样结构域与人 IgG1 的 Fc 部分融合而成,并报告称它们表现出小眼症。在此,用 PRV 攻击表达融合蛋白的两个转基因小鼠系,以将它们的抗性与表达不同类型融合蛋白的转基因小鼠的抗性进行比较。令人惊讶的是,两种转基因小鼠系都表现出对病毒感染的高度抵抗力,尤其是通过注射途径感染。路线。还观察到胚胎成纤维细胞的显着抵抗力。总而言之,这些发现表明,由与人 Fc 部分融合的第一个 Ig 样结构域组成的融合蛋白为转基因小鼠提供了对 PRV 感染的显着抵抗力。
Nectin‐1 is a Ca2+‐independent Ig‐like cell–cell adhesion molecule and an alphaherpesvirus receptor that binds to virion glycoprotein D by the first Ig‐like domain. We have investigated the antiviral potentials of soluble forms of porcine nectin‐1 to PRV infection by generating transgenic mice expressing different types of fusion protein. Previously, we reported that mice transgenic for a chimera that carried the entire ectodomain of porcine nectin‐1 fused to the Fc portion of porcine IgG1 were more resistant than those transgenic for a chimera that carried the first Ig‐like domain fused to the Fc portion. Recently, we generated transgenic mice expressing a fusion protein made of the first Ig‐like domain fused to the Fc portion of human IgG1, and reported that they showed a microphthalmia. Here, two transgenic mouse lines expressing the fusion protein were challenged with PRV for comparing their resistances with those of transgenic mice expressing different types of fusion protein. Surprisingly, both transgenic mouse lines showed a high resistance to the viral infection, especially via the i.n. route. Significant resistance of the embryonic fibroblasts was also observed. Altogether, these findings indicated that the fusion protein consisting of the first Ig‐like domain fused to the human Fc portion provided a marked resistance against PRV infection to the transgenic mice.
DOI: 10.1006/viro.1998.9218
发表时间: 1998-06-20
期刊: VIROLOGY
影响因子: 3.7
作者:
Warner, MS;Geraghty, RJ;Spear, PG
通讯作者: Spear, PG
DOI: 10.1099/0022-1317-75-6-1211
发表时间: 1994-06-01
影响因子: 3.8
作者:
HEROLD, BC;VISALLI, RJ;SPEAR, PG
通讯作者: SPEAR, PG
DOI: 10.1126/science.280.5369.1618
发表时间: 1998-06-05
期刊: SCIENCE
影响因子: 56.9
作者:
Geraghty, RJ;Krummenacher, C;Spear, PG
通讯作者: Spear, PG