新型细胞因子PGRN抑制A型流感病毒增殖的分子机制

Influenza virus is an important zoonotic pathogen, which is a threat to the safety of animal husbandry and human public health. Therefore, it has a great significance to investigate the host regulatory factors required for influenza virus infection for the study of virus pathogenesis and new anti-viral drugs. Progranulin (PGRN) as a new cytokine plays a crucial role in several physiological and pathological process, including host defense and innate antiviral factor. Howener the immune mechanism of PGRN in influenza virus infection is still not clear. Our previous results suggested that elevated expression of PGRN was induced by influenza virus infection in lung tissue and PGRN-deficient mice was susceptible to influenza virus infection than wild-type mice, and the polymerase level of virus in lung tissue was higher than wild-type mice. Based on our previous results, we will evaluate the effect of PGRN on influenza virus multiplication and examine the PGRN-mediated anti-viral signaling pathways. The project will provide new sight for the mechanism of influenza virus infection and new target for the study of anti-viral drugs.

流感病毒是重要的人畜共患病病原，不仅威胁畜牧业的生产安全，而且严重危害人类的健康。研究流感病毒感染过程中的宿主调控因子，对阐明流感病毒的致病机理和研发新型抗流感病毒药物具有十分重要的科学意义。新型细胞因子PGRN在多种生理和病理过程中都发挥作用，具有防御宿主感染和天然抗病毒因子的作用。但PGRN在流感病毒感染中的免疫机理还不清楚。我们的前期实验结果发现，流感病毒感染能够诱导肺组织PGRN上调表达，PGRN基因缺失小鼠对流感病毒感染的易感性增加，基因缺失小鼠肺组织中病毒聚合酶的水平升高。在前期研究结果的基础上，本项目拟评价PGRN在流感病毒增殖中的作用，揭示PGRN介导的抗病毒信号通路。该研究将为流感病毒感染机制的解析和抗病毒药物的设计等提供新的理论基础。