Pathological study of snyder hill strain in acute canine distemper virus infection in transgenic mice bearing dog signaling lymphocytic activation molecule (DogSlam)

Canine Distemper Virus (CDV), member of Genus Morbilivirus, caused canine distemper disease, the most important viral disease of dogs with high mortality rate. The objective of this study was to verify acute canine distemper virus, Snyder Hill strain, infection in transgenic mice bearing DogSLAM (canine signaling lymphocyte activation molecule, CD150), as a susceptible host for the pathological study of canine distemper in vivo. F1 Transgenic mice, positive of DogSLAM tag receptor, 3 and 12 weeks old, both male and female were divided into 4 groups. Group 1 (control group, 4 mice); Dulbecco’s modified eagle’s medium (DMEM) inoculation. The CDV, Snyder Hill strain, was inoculated at 1x10 [superscript 5] TCID [subscript 50] by different routes in each groups as follow, group 2; intranasal inoculation ( 6 mice), group 3; intracerebral inoculation (6 mice) and group 4; intraperitoneal inoculation (5 mice). Clinical signs of experimental transgenic mice were observed at 12 and 24 hours post infection and daily monitored until 14 days post-infection. Others parameters included weight, conjunctival swab for detection viral inclusion body, blood profile, necropsy and histopathology of various visceral organs, immunohistochemistry for detection of CDV and anti-hemagglutinin (HA) antigen, RT-PCR for detection of CDV and virus isolation, were subsequently performed. All observed parameters showed negatively results of Snyder Hill strain CDV infection in transgenic mice bearing DogSLAM gene. In conclusion, the results from this study were unable to elucidate for CDV infection in comparison with the tissue culture study. However, further investigation about factors that related to SLAM gene expression for study of CDV infection in animal model should be concerned and investigated.

犬瘟热病毒（Canine Distemper Virus, CDV）为麻疹病毒属（Genus Morbillivirus）成员，可引发犬瘟热，这是犬类中致死率极高的最重要病毒性疾病之一。本研究旨在验证携带犬SLAM（犬信号淋巴细胞活化分子，canine signaling lymphocyte activation molecule, CD150）的转基因小鼠，能否作为易感宿主用于急性犬瘟热病毒斯奈德希尔株（Snyder Hill strain）感染的体内病理研究。本研究选取犬SLAM受体阳性的F1代转基因小鼠，涵盖3周龄、12周龄两个年龄段，雌雄各半，共分为4组：第1组为对照组（4只），接种杜氏改良伊格尔培养基（Dulbecco’s Modified Eagle’s Medium, DMEM）；第2至4组以1×10⁵ TCID₅₀的斯奈德希尔株犬瘟热病毒经不同途径接种：第2组经鼻内接种（6只），第3组经脑内接种（6只），第4组经腹腔接种（5只）。于感染后12小时、24小时观察实验转基因小鼠的临床症状，并每日监测直至感染后14天。后续还开展了多项检测分析：体重监测、结膜拭子检测病毒包涵体、血液学检测、剖检及多种内脏器官的组织病理学检查、检测犬瘟热病毒与抗血凝素（HA）抗原的免疫组化实验、逆转录聚合酶链式反应（RT-PCR）检测犬瘟热病毒及病毒分离。所有观测参数均显示，携带犬SLAM基因的转基因小鼠未出现斯奈德希尔株犬瘟热病毒感染相关的阳性反应。综上，本研究结果未能阐明该病毒的感染情况，与组织培养研究结果存在差异。未来应关注并深入探究与SLAM基因表达相关的影响因素，以开展动物模型中的犬瘟热感染研究。