PDF(Pubmed)
Abstract：
Lassa virus (LASV), an arenavirus endemic to West Africa, causes Lassa fever-a lethal hemorrhagic fever. Entry of LASV into the host cell is mediated by the glycoprotein complex (GPC), which is the only protein located on the viral surface and comprises three subunits: glycoprotein 1 (GP1), glycoprotein 2 (GP2), and a stable signal peptide (SSP). The LASV GPC is a class one viral fusion protein, akin to those found in viruses such as human immunodeficiency virus (HIV), influenza, Ebola virus (EBOV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These viruses are enveloped and utilize membrane fusion to deliver their genetic material to the host cell. Like other class one fusion proteins, LASV-mediated membrane fusion occurs through an orchestrated sequence of conformational changes in its GPC. The receptor-binding subunit, GP1, first engages with a host cell receptor then undergoes a unique receptor switch upon delivery to the late endosome. The acidic pH and change in receptor result in the dissociation of GP1, exposing the fusion subunit, GP2, such that fusion can occur. These events ultimately lead to the formation of a fusion pore so that the LASV genetic material is released into the host cell. Interestingly, the mature GPC retains its SSP as a third subunit-a feature that is unique to arenaviruses. Additionally, the fusion domain contains two separate fusion peptides, instead of a standard singular fusion peptide. Here, we give a comprehensive review of the LASV GPC components and their unusual features.
摘要：
拉沙病毒(LASV)一种西非特有的沙粒病毒，引起拉沙热——一种致命的出血热。LASV进入宿主细胞是由糖蛋白复合物（GPC）介导的，它是唯一位于病毒表面的蛋白质，包含三个亚基：糖蛋白1（GP1），糖蛋白2（GP2），和稳定的信号肽(SSP)。LASVGPC是一类病毒融合蛋白，类似于在人类免疫缺陷病毒（HIV）等病毒中发现的病毒，流感,埃博拉病毒（EBOV）和严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）。这些病毒被包膜并利用膜融合将其遗传物质递送至宿主细胞。像其他一类融合蛋白一样，LASV介导的膜融合通过其GPC中构象变化的协调序列发生。受体结合亚基，GP1首先与宿主细胞受体接合,然后在递送至晚期核内体时经历独特的受体转换。酸性pH和受体的变化导致GP1的解离，暴露融合亚基，GP2，这样可以发生融合。这些事件最终导致融合孔的形成,使得LASV遗传物质被释放到宿主细胞中。有趣的是,成熟的GPC保留了其SSP作为第三个亚基-这是沙粒病毒独有的特征。此外,融合域包含两个独立的融合肽，而不是标准的单一融合肽。这里,我们全面回顾了LASVGPC组件及其不寻常的特征。
