非洲猪瘟病毒p22蛋白拮抗宿主抗病毒天然免疫应答的分子机制

非洲猪瘟（ASF）是由非洲猪瘟病毒（ASFV）感染引起的高度致死性猪传染病，目前尚无针对该病的有效疫苗和治疗手段。ASFV感染和免疫逃逸机制不明确，是阻碍疫苗研制进程的重要原因。申请人以宿主天然免疫系统清除入侵病毒最为重要的I型IFN信号通路为切入点，对调控该通路激活的病毒蛋白进行了系统筛选和功能验证，以期进一步阐明ASFV免疫逃逸机制。本项目选择显著抑制I型IFN信号通路激活的p22蛋白进行深入探讨。p22蛋白是ASFV内囊膜结构蛋白，目前尚无该蛋白调控宿主抗病毒天然免疫应答的报道。我们将继续探究p22蛋白在ASFV逃逸宿主抗病毒天然免疫反应中的作用，寻找p22蛋白的分子靶标，进而解析p22蛋白在ASFV感染过程中的功能和作用机理。该项目的顺利完成将有助于揭示ASFV感染与免疫逃逸新策略，亦将为临床治疗药物和新型高效疫苗的研发提供理论依据和分子靶标。

African swine fever (ASF), caused by African swine fever virus (ASFV), is a highly contagious disease of swine with mortality approaching 100%. The epidemic of ASF in China has brought great threats to the development of the pig industry, and no efficient vaccines and therapeutic are available up to now. Recently, researches focusing on characteristics, immune evasion and pathogenesis of ASFV have been carried out. Whereas large gaps in knowledge concerning viral proteins and their mechanisms responsible for immune evasion severely hindered the development of vaccines. To identify candidate molecules involved in type I IFN-triggered innate immune responses, we screened 179 ASFV proteins for their abilities to regulate IFN-β-mediated activation of STAT1/2 in reporter assays. Our results showed that p22 protein, the inner envelope structural protein of ASFV, significantly inhibited IFN-β-induced transcription of interferon-stimulated genes and activation of STAT1/2 promoter. In this proposal, we aim to decode the mechanisms underlying p22-mediated inhibition of host antiviral immunity and dissect the novel function of p22, which will be great helpful for better illustrating the immune evasion mechanisms and pathogenesis of ASFV. These efforts will also contribute to the development of vaccines and therapeutic against ASF.