CDV强毒株H蛋白抑制β干扰素产生的分子机制

Canine distemper virus (CDV) hemagglutinin (H) protein plays an important role in virus infection, pathogenicity and immunosuppression. The virulence of the virus is closely related to the ability of the virus to escape the host immune response. The H protein of virulent CDV inhibited β interferon-inducing activity to a far greater extent than attenuated CDV. The detail mechanisms by which the primary β interferon-inducing activity is impaired by H protein of virulent CDV still remain unexplained. In this study, the specific signal pathways and the key molecules acting on signaling pathway, which were inhibited and targeted by virulent CDV H protien, were identified and screened. The interaction mechanisms of the key molecules and virulent CDV H protein were analyzed. The key domains and amino acids mutation of CDV H protein, which were responsible for suppression of β interferon-induction activity, were identified. This will provide direct esperimental evidences to understand the pathological mechanism and host-virus interaction in CDV infection, which will be very important for the development of novel antiviral drugs and vaccines for the prevention of CDV infection.

犬瘟热病毒（CDV）血凝素（H）蛋白在病毒感染、致病性和免疫抑制等方面发挥重要作用。病毒致病性的强弱与病毒逃逸宿主免疫应答的能力密切相关。前期研究显示，与CDV弱毒株相比，CDV强毒株H蛋白能够显著抑制β干扰素的产生，但是详细机制不明。本项目鉴定CDV强毒株H蛋白抑制β干扰素产生的具体信号通路，筛选CDV强毒株H蛋白作用的β干扰素信号通路关键靶标分子；进一步分析CDV强毒株H蛋白与β干扰素产生信号通路关键靶标分子的作用机制；鉴定CDV强毒株H蛋白抑制β干扰素产生的关键结构域，比较CDV强弱毒株在该结构域的氨基酸变异，探寻影响CDV H蛋白抑制β干扰素产生的氨基酸变异位点。通过上述研究，阐明CDV强毒株H蛋白抑制β干扰素产生的分子机制，进一步了解免疫抑制疾病的发病机制，为诊断、预防和治疗免疫抑制疾病提供理论基础和药物靶点。