Lee Sungjin, Chung Yoon Hee, Lee Choongho
College of Pharmacy, Dongguk University, Goyang 10326, Republic of Korea.
Department of Anatomy, College of Medicine, Chung-Ang University, Seoul 06974, Republic of Korea.
Biomol Ther (Seoul). 2017 Jan 1;25(1):69-79. doi: 10.4062/biomolther.2016.208.
Viruses continue to evolve a new strategy to take advantage of every aspect of host cells in order to maximize their survival. Due to their central roles in transducing a variety of transmembrane signals, GPCRs seem to be a prime target for viruses to pirate for their own use. Incorporation of GPCR functionality into the genome of herpesviruses has been demonstrated to be essential for pathogenesis of many herpesviruses-induced diseases. Here, we introduce US28 of human cytomegalovirus (HCMV) as the beststudied example of virally-encoded GPCRs to manipulate host GPCR signaling. In this review, we wish to summarize a number of US28-related topics including its regulation of host signaling pathways, its constitutive internalization, its structural and functional analysis, its roles in HCMV biology and pathogenesis, its proliferative activities and role in oncogenesis, and pharmacological modulation of its biological activities. This review will aid in our understanding of how pathogenic viruses usurp the host GPCR signaling for successful viral infection. This kind of knowledge will enable us to build a better strategy to control viral infection by normalizing the virally-dysregulated host GPCR signaling.
病毒不断进化出新策略，利用宿主细胞的各个方面以实现自身生存最大化。由于G蛋白偶联受体（GPCR）在转导多种跨膜信号中发挥核心作用，它们似乎成为病毒“盗用”以供自身利用的主要目标。已证明将GPCR功能整合到疱疹病毒基因组中对许多疱疹病毒引起疾病的发病机制至关重要。在此，我们介绍人类巨细胞病毒（HCMV）的US28，它是研究最为深入的病毒编码GPCR，用于操纵宿主GPCR信号传导。在本综述中，我们希望总结一些与US28相关的主题，包括其对宿主信号通路的调节、其组成型内化、其结构和功能分析、其在HCMV生物学和发病机制中的作用、其增殖活性和在肿瘤发生中的作用，以及对其生物学活性的药理学调节。本综述将有助于我们理解致病性病毒如何篡夺宿主GPCR信号以实现成功的病毒感染。这类知识将使我们能够制定更好的策略，通过使病毒失调的宿主GPCR信号正常化来控制病毒感染。
