犬瘟热病毒（CDV）作为“头号杀手”严重威胁大熊猫的生命健康及种群安全。陕西省珍稀野生动物抢救饲养研究中心暴发的犬瘟热疫情共造成5只大熊猫感染死亡。我们发现大熊猫源犬瘟热病毒giant panda/SX/2014H蛋白与宿主SLAM受体结合的549位关键氨基酸位点由犬源分离株Tyr（Y）突变为（H），推测H蛋白Y549H替换导致giant panda/SX/2014获得了跨种传播能力，且毒力增强。本研究拟以病毒与受体相互作用为出发点，以氨基酸定点突变、反向遗传学操作为主要技术手段，表达大熊猫SLAM受体的转基因小鼠为感染模型，分别在蛋白水平、细胞感染水平、动物模型上明确H蛋白Y549H突变对受体亲和力、H/F相互作用力、细胞增殖特性以及转基因小鼠致病性的影响，阐明CDV大熊猫分离株跨宿主感染及致病性增强的分子基础，为有效防控大熊猫犬瘟热、维护大熊猫种群安全提供理论依据。

As the number one killer of giant pandas, Canine distemper virus (CDV) poses a serious threat to their health and population safety. Over the period of December, 2014 through April, 2015, five of six CDV infected giant pandas died in the Shaanxi Rare Wild Animal Rescue and Research Center, China. The occurrence of the Y549H substitution of the CDV isolate giant panda/SX/2014 has aroused our attention, as it is involved in hemagglutinin (H) protein binding to the signaling lymphocytic activation molecule (SLAM) receptor and has been implicated in the emergence of highly pathogenic CDV and host range expansion. In this project we intend to take the perspective of the virus-receptor interaction to evaluate the influence of the Y549H substitution on receptor affinity, interaction of H/F, cell proliferation characteristic and pathogenicity both in vitro and in vivo by employing site-directed mutation, reverse genetics technique and CDV infected mice model which was established by transgenic mice expressing giant panda SLAM receptor previously. The results of these studies will clarify the molecular determinants of cross species-transmission and pathogenicity enhancement of giant panda/SX/2014 and provide theoretical basis for effective prevention and control of canine distemper for successful conservation of this endangered species.