致病性新世界沙粒病毒是一类鼠源RNA包膜病毒，Machupo病毒是其中一员。此类病毒感染人时对转铁蛋白受体1（TfR1）的利用决定了其致病性，然而其中机理尚不明确。我们推测，病毒挟持TfR1转运至晚期内体从而偏离早期内体是原因之一。深入研究Machupo等致病性新世界沙粒病毒在早/晚期内体间的转运过程并解析与此相关的重要宿主因子，将对解释其致病性和发现针对病毒进入阶段的药物干预靶点具有重要意义。本项目拟在细胞成像技术的基础上辅以组学分析，试图明晰病毒粒子在早/晚期内体间的转运过程，并发现参与此过程的重要宿主因子，阐明其对内体转运和病毒进入的影响，最终解释内体转运与此类病毒致病性的关系。开展本研究有助于阐明沙粒病毒进入靶细胞的过程机制，为深入了解此类病毒的致病性提供理论依据。

Pathogenic New World arenaviruses are a kind of rat-derived, enveloped, RNA virus, and Machupo virus is included. They use human transferrin receptor 1 (TfR1) to infect human, which determines their pathogenicity. However, the underlying mechanism remains unclear. Here, we presume that virion hijacks TfR1 trafficking to the late endosome, which deviates from the early endosome, is one of the reasons to that. Hence, thoroughly studying the virion transporting pathway between the early and late endosome and analyzing the important host factors involving in, is of great importance for elaborating the pathogenicity and discovering new intervention targets. Our study will adopt transcriptomics in addition to cell imagining technologies, firstly try to figure out the virion transport between the early and late endosome, then discover the important host factors involving in, next clarify their influence on the endosome trafficking and virion entry, finally explain the relationship between the endosome trafficking and pathogenicity. This study is beneficial to illuminate the process of arenavirus entry, and provide theoretical basis for the pathogenicity of arenavirus.