中文摘要
猪流感病毒具有重要的公共卫生学意义,猪流感病毒感染后诱导宿主干扰素及炎性因子表达,干扰素的抗病毒机制主要通过其下游诱导效应因子而发挥作用。IFI35属于新的干扰素诱导效应因子,其生物学功能尤其是其在病毒感染过程中的作用机制尚不清楚。本研究拟分析干扰素诱导效应因子IFI35在猪流感病毒感染后的表达变化、亚细胞定位变化、对病毒复制的功能分析、与流感病毒NS1蛋白的相互作用分析以及在调控RIG-I介导的IFNβ激活通路上的功能分析,揭示IFI35在调节宿主流感病毒感染的应答反应与分子机制,丰富人们对干扰素效应因子在抗病毒感染过程中的功能认知。
英文摘要
Swine influenza viruses have important public health significance.Host cells can express a series of interferon and inflammatory cytokines after swine influenza virus infection. The interferon play antiviral functions mainly through its downstream effectors. IFI35 is a newly interferon induced effector, however, its biological function especially in the mechanism of regulating viral infection is unclear. This study analyzes the changes of IFI35 expression and subcellular localization during swine influenza virus infection.We also interested its function in swine influenza virus replication, and its interaction with the virus nonstructural protein NS1. NS1 is well known as an interferon antagonist and it can bind with RIG-I during influenza virus infection. The aim of this study is to investigate the role of IFI35 in regulating RIG-I-mediated IFNβ activation pathway during swine influenza virus infection.This study can provide the molecular mechanism of IFI35 in the regulating host cells response to swine influenza virus infection and enrich people's awareness of the function of interferon-induced effectors during anti-virus process.
结题摘要
A型流感病毒能够在不同物种间传染,并造成流行。流感病毒进入宿主体内首先被宿主先天免疫系统识别,通过胞内信号转导通路的激活,刺激干扰素(IFNs)和干扰素诱导基因(ISGs)的活性等一系列细胞信号转导事件来抑制病毒复制。然而,关于干扰素诱导基因在猪流感病毒感染过程的功能,目前还鲜有报道。在本研究中,我们发现干扰素诱导蛋白IFI35通过结合猪流感病毒H3N2非结构蛋白NS1来抑制猪流感病毒复制。在A549细胞中过表达IFI35能显著提高猪流感病毒H3N2诱导干扰素的产生和抑制猪流感病毒的复制,相反,沉默IFI35表达后却明显促进猪流感病毒H3N2的复制。IFI35与H3N2亚型猪流感病毒NS1的结合破坏了NS1与RIG-I的结合,抑制了RIG-I K48连接的泛素化修饰,激活了RIG-I介导的干扰素的产生。这些数据揭示了宿主IFI35拮抗H3N2亚型猪流感病毒复制的作用。
