Gamma interferon (IFN-γ) receptor null-mutant mice are more susceptible to herpes simplex virus type 1 infection than IFN-γ ligand null-mutant mice
Gamma interferon (IFN-γ) receptor null-mutant mice are more susceptible to herpes simplex virus type 1 infection than IFN-γ ligand null-mutant mice
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DOI：
10.1128/jvi.73.6.5196-5200.1999
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发表时间：
1999-06-01
影响因子：
5.4
通讯作者：
Clarke, K
中科院分区：
文献类型：
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作者：
Cantin, E;Tanamachi, B;Clarke, K
已经对在γ干扰素基因（Ifng）或γ干扰素受体基因（Ifngr）中具有无效突变的小鼠品系进行了工程改造。使用这些菌株作为病毒和细菌感染的动物模型，增强了我们对γ干扰素（IFN-γ）在宿主免疫应答中的作用的理解。然而，Ifng（-/-）（GKO）和Ifngr（-/-）（RGKO）小鼠之间的直接比较是有问题的，因为这些小鼠的先前可用品系具有不同的遗传背景（即，GKO小鼠为C57 BL/6和BALB/c，RGRO小鼠为129/Sv//Ev）。为了能够直接比较GKO和RGKO小鼠中单纯疱疹病毒1型（HSV-1）感染，我们将IFN-γ无效突变引入129/Sv//Ev背景。我们报告，HSV-1接种后，RGRO小鼠的死亡率显著高于GKO小鼠（38%对23%，P = 0.0001）。类似地，RGKO小鼠中牛痘病毒攻击的死亡率显著高于GKO小鼠。排除遗传背景差异作为混杂问题，这些结果与IFN-γ受体的替代配体的存在一致，该替代配体也能够介导针对病毒攻击的保护。
Mouse strains with null mutations in the gamma interferon gene (Ifng) or the gamma interferon receptor gene (Ifngr) have been engineered. The use of these strains as animal models of viral and bacterial infections has enhanced our understanding of the role of gamma interferon (IFN-gamma) in the host immune response. However, direct comparisons between Ifng(-/-) (GKO) and Ifngr(-/-) (RGKO) mice have been problematic because previously available strains of these mice have had different genetic backgrounds (i.e., C57BL/6 and BALB/c for GKO mice and 129/Sv//Ev for RGRO mice). To enable direct comparison of herpes simplex virus type 1 (HSV-1) infections in GKO and RGKO mice, we introduced the IFN-gamma null mutation into the 129/Sv//Ev background. We report that, after HSV-1 inoculation, mortality was significantly greater in RGRO mice than in GKO mice (38 versus 23%, P = 0.0001). Similarly, the mortality from vaccinia virus challenge was significantly greater in RGKO mice than in GKO mice. With differences in genetic background excluded as a confounding issue, these results are consistent with the existence of an alternative ligand(s) for the IFN-gamma receptor that is also capable of mediating protection against viral challenge.