Department of Biology, Stanford University, Stanford, California 94305.
Department of Genetics, Stanford University, Stanford, California 94305.
Cold Spring Harb Perspect Biol. 2020 Mar 2;12(3):a034090. doi: 10.1101/cshperspect.a034090.
Viruses are obligate intracellular parasites that rely on their hosts for protein synthesis, genome replication, and viral particle production. As such, they have evolved mechanisms to divert host resources, including molecular chaperones, facilitate folding and assembly of viral proteins, stabilize complex structures under constant mutational pressure, and modulate signaling pathways to dampen antiviral responses and prevent premature host death. Biogenesis of viral proteins often presents unique challenges to the proteostasis network, as it requires the rapid and orchestrated production of high levels of a limited number of multifunctional, multidomain, and aggregation-prone proteins. To overcome such challenges, viruses interact with the folding machinery not only as clients but also as regulators of chaperone expression, function, and subcellular localization. In this review, we summarize the main types of interactions between viral proteins and chaperones during infection, examine evolutionary aspects of this relationship, and discuss the potential of using chaperone inhibitors as broad-spectrum antivirals.
病毒是专性细胞内寄生虫，依赖宿主进行蛋白质合成、基因组复制和病毒颗粒生产。因此，它们进化出了多种机制来转移宿主资源，包括分子伴侣，促进病毒蛋白的折叠和组装，在持续的突变压力下稳定复杂结构，并调节信号通路以抑制抗病毒反应并防止宿主过早死亡。病毒蛋白的生物发生常常给蛋白质稳态网络带来独特的挑战，因为它需要快速协调地产生大量数量有限的多功能、多域和易聚集的蛋白质。为了克服这些挑战，病毒不仅作为客户与折叠机制相互作用，还作为伴侣蛋白表达、功能和亚细胞定位的调节剂。在这篇综述中，我们总结了感染过程中病毒蛋白与伴侣之间的主要相互作用类型，考察了这种关系的进化方面，并讨论了使用伴侣蛋白抑制剂作为广谱抗病毒药物的潜力。
