INSERM UMR 1231, Labex LipSTIC, Faculty of Health Sciences, Université de Bourgogne Franche-Comté, Dijon, France.
University Hospital of Dijon, Dijon, France.
Microbiol Mol Biol Rev. 2021 Dec 15;85(4):e0003521. doi: 10.1128/MMBR.00035-21. Epub 2021 Oct 13.
Viruses are intracellular parasites that subvert the functions of their host cells to accomplish their infection cycle. The endoplasmic reticulum (ER)-residing chaperone proteins are central for the achievement of different steps of the viral cycle, from entry and replication to assembly and exit. The most abundant ER chaperones are GRP78 (78-kDa glucose-regulated protein), GRP94 (94-kDa glucose-regulated protein), the carbohydrate or lectin-like chaperones calnexin (CNX) and calreticulin (CRT), the protein disulfide isomerases (PDIs), and the DNAJ chaperones. This review will focus on the pleiotropic roles of ER chaperones during viral infection. We will cover their essential role in the folding and quality control of viral proteins, notably viral glycoproteins which play a major role in host cell infection. We will also describe how viruses co-opt ER chaperones at various steps of their infectious cycle but also in order to evade immune responses and avoid apoptosis. Finally, we will discuss the different molecules targeting these chaperones and the perspectives in the development of broad-spectrum antiviral drugs.
病毒是细胞内寄生虫，它们颠覆宿主细胞的功能来完成感染周期。内质网（ER）驻留的伴侣蛋白是实现病毒周期不同步骤的核心，从进入、复制到组装和释放。最丰富的 ER 伴侣蛋白包括 GRP78（78kDa 葡萄糖调节蛋白）、GRP94（94kDa 葡萄糖调节蛋白）、碳水化合物或凝集素样伴侣蛋白 calnexin（CNX）和 calreticulin（CRT）、蛋白二硫键异构酶（PDIs）和 DNAJ 伴侣蛋白。这篇综述将重点介绍 ER 伴侣蛋白在病毒感染过程中的多效性作用。我们将涵盖它们在病毒蛋白折叠和质量控制中的重要作用，特别是在宿主细胞感染中起主要作用的病毒糖蛋白。我们还将描述病毒如何在其感染周期的各个步骤中以及为了逃避免疫反应和避免细胞凋亡而利用 ER 伴侣蛋白。最后，我们将讨论针对这些伴侣蛋白的不同分子以及开发广谱抗病毒药物的前景。
