内吞相关lncNRAV/Rab5c介导囊泡转运促进呼吸道病毒增殖的作用研究

呼吸道感染病毒分无包膜与有包膜两类，通常前者以内吞途径进入细胞，后者则以受体识别、膜融合为主，部分也可发生内吞。在前期工作中，我们发现长链非编码RNA NRAV与呼吸道病毒感染高度相关，其靶分子为Rab5c；无包膜病毒感染可引起NRAV及Rab5c升高，而有包膜病毒则不明显，甚至降低; 在过表达NRAV的细胞中感染病毒，1小时即可见Rab5c与病毒发生共定位，病毒复制增加。已知Rab5c为早期内体的标志蛋白，介导囊泡内吞、融合、转运等，故推断病毒内吞进入细胞可诱导NRAV和Rab5c表达，进而增加病毒内体转运，促病毒增殖。本研究将应用无包膜及有包膜呼吸道病毒，利用转基因及基因敲除等手段，体内、外研究内吞行为对NRAV和Rab5c表达的影响及可能的通路，探讨它们对病毒进入细胞、复制和其他生命活动的作用及机制。该研究为探索病毒与宿主相互作用提供了新视角，为开发潜在的抗病毒靶点提供新思路。

Respiratory viruses can be divided into two types, i.e. unenveloped and enveloped. Usually, the former enters the cells by endocytosis, while the latter mainly focuses on receptor recognition and membrane fusion, and some endocytosis can also occur. Our previous study has shown that lnc NRAV was highly related to respiratory virus infection, and its target molecule was Rab5c. Non-enveloped virus infection can cause the increase of NRAV and Rab5c, while it was not obvious or even decreased during enveloped virus infection. Confocal microscopy showed that some of the virus was colocalized with Rab5c positive vacuoles in the cytoplasm 1 h post infection in NRAV-overexpressed cells, and the virus replication was also increased. It is known that Rab5c is a marker protein of early endosome, which mediates vesicle endocytosis, fusion, transport and so on. Therefore, it is inferred that viral endocytosis could induce the expression of NRAV and Rab5c, and then increase viral endosome transport and finally promote virus proliferation. To explore their effects and mechanisms on virus entry, replication and other life activities, in this study, unenveloped and enveloped respiratory viruses will be used to explore the effects and pathways of vesicle transportation related with NRAV/Rab5c in vivo and in vitro by means of transgenic and gene knockout . This study might provide a new perspective study of virus-host interaction and contribute to the discovery of potential antiviral targets.