RIG-I信号通路相关基因多态性与发热伴血小板减少综合征病毒感染发生风险和严重程度的相关性及机制研究

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a newly identified bunyavirus. Clinical symptoms and outcomes of SFTSV infection in humans varied, some patients only with self-limited symptom such as fever, while 15% of the cases dead with bleeding tendency or multiple organ failure. Epidemiological survey showed that the infection and outcomes of SFTSV infection in humans may be associated with genetic background difference, but the underlying mechanism is still unknown. Recent studies showed that RIG-I signal pathway plays a key role in inducing type I interferon for host cells to resist SFTSV infection. Recent researches also suggested that the susceptibility and severity of some RNA virus infection in humans could be affected by polymorphisms of RIG-I signal pathway related genes. In this study, we proposed to choose RIG-I signal pathway genes related SNPs of Han population by screening HapMap database, and analyze the correlation between the selected SNPs and the susceptibility or severity of SFTSV infection through the cases-controls and cases-cases association studies. And then determine the roles related SNPs play in affecting SFTSV infection in humans, using the technology of molecular biology and virology. And eventually reveal the underlying genetic mechanism influencing individual susceptibility and the outcome of SFTSV infection. Hope that through this study, we could obtain some susceptibility genes and SNPs which could be used as new parameters for early warning and prevention of SFTSV infection.

发热伴血小板减少综合征病毒（SFTSV）是近年我国发现的新型布尼亚科病毒。该病毒感染人引起的症状个体差异较大，部分病人仅出现发热等自限性症状，而约15%的病例会因出血倾向或多器官衰竭而死亡。流行病学调查显示，SFTSV感染和预后与遗传背景有关，而其作用机制尚不明朗。最近的研究表明RIG-I信号通路对宿主细胞抵抗SFTSV感染时I型干扰素的诱导起着关键作用，而该信号通路相关基因多态性与多种RNA病毒的感染和预后相关。据此，本项目拟筛选HapMap数据库中汉族人群RIG-I信号通路相关基因多态性位点（SNPs），通过基因型检测和病例-对照、病例-病例关联分析，阐明与SFTSV感染的发生风险和严重程度相关联的SNPs基因型和单倍型；然后，采用表型检测和功能验证试验探索关联SNPs的功能机制。希望通过此项研究，获得具有应用价值的易感基因和SNPs，为SFTSV感染高危人群的预警和预防提供新的指标。

发热伴血小板减少综合征病毒（SFTSV）是近年我国发现的新型布尼亚科病毒。该病毒感染人引起的症状个体差异较大，部分病人仅出现发热等自限性症状，而约15%的病例会因出血倾向或多器官衰竭而死亡。流行病学调查显示，SFTSV感染和预后与遗传背景有关，而其作用机制尚不明朗。最近的研究表明RIG-I信号通路对宿主细胞抵抗SFTSV感染时I型干扰素的诱导起着关键作用，而该信号通路相关基因多态性与多种RNA病毒的感染和预后相关。本项目筛选了HapMap数据库中汉族人群RIG-I信号通路相关基因多态性位点（SNPs），通过基因型检测和病例-对照、病例-病例关联分析，阐明了与SFTSV感染的发生风险和严重程度相关联的SNPs基因型和单倍型；然后，采用表型检测和功能验证试验探索关联SNPs的功能机制。通过此项研究，获得了具有应用价值的易感基因和SNPs，为SFTSV感染高危人群的预警和预防提供新的指标。