10 年9月广东东莞暴发国内首起社区聚集性基孔肯雅热疫情，打破我国长期以散在输入为特征的流行特点，为其防控带来挑战。迄今对该疫情CHIKV变异分子演化和致病免疫机制及群体感染特征缺乏系统研究。课题组前期从流行病学角度进行初步分析，发现感染者轻重症不同程度和阶段各细胞因子存在差异，但机制未明。基于此，本课题拟开展1）对CHIKV进行时空演化分析，探讨病毒来源与变异规律；2）以病毒C-E基因序列为目的基因，利用毕赤酵母表达体系构建基孔肯雅病毒样颗粒（CHIKV-VLPs），在动物模型上评价免疫学功效；3）利用绿色荧光修饰CHIKV-VLPs建立感染与转译示踪平台，在细胞和动物模型上探讨感染与免疫的分子机制；4）追踪感染者在急性期、恢复期不同阶段炎症因子、趋化因子和免疫相关分子的变异情况，分析轻、重症和不同阶段转归之间的关系，阐述其致病感染免疫机制。研究结果对基孔肯雅热的防控提供关键科学依据。

A Chikungunya fever epidemic outbroke in a Dongguan community in Guangdong Province in China in September 2010, which broke the scattered-input epidemic feature in China and brought challenge to disease control. Heretofore, the molecular mutational evolution of CHIKV and the feature of population infection remain to be demonstrated. Our study group conducted a preliminary analysis about the epidemic feature and found out variation in the severity of syndrome and cytokine expression, but the mechanism remained unknown. Based on the condition mentioned, our study group is planning to conduct studies about: 1) The spatial-temporal evolution characteristics of CHIKV, to investigate the origin and the variation of CHIKV; 2) The Immunological efficacy in animal model, using Pichia pastoris expression system the targeted viral C-E sequence to construct CHIKV-VLPs; 3) The molecular mechanism of infection and immunity in cellular and animal model, using infection and transcription platform based on green fluorescence modulated CHIKV-VLPs; 4) The variation of cytokine expression in different clinical stages, to analyze the relation between severity and the switch of different clinical stages and to demonstrate the immunologic mechanism of the CHIKV infection.