De Groof Timo W M, Elder Elizabeth G, Siderius Marco, Heukers Raimond, Sinclair John H, Smit Martine J
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium (T.W.M.D.G.); Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (E.G.E., J.H.S.); Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands (M.S., R.H., M.J.S.); and QVQ Holding B.V., Utrecht, The Netherlands (R.H.).
In Vivo Cellular and Molecular Imaging Laboratory (ICMI), Vrije Universiteit Brussel, Brussels, Belgium (T.W.M.D.G.); Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom (E.G.E., J.H.S.); Division of Medicinal Chemistry, Faculty of Sciences, Amsterdam Institute for Molecular and Life Sciences (AIMMS), Vrije Universiteit Amsterdam, Amsterdam, The Netherlands (M.S., R.H., M.J.S.); and QVQ Holding B.V., Utrecht, The Netherlands (R.H.)
Pharmacol Rev. 2021 Apr;73(2):828-846. doi: 10.1124/pharmrev.120.000186.
Herpesviruses are ubiquitous pathogens that establish lifelong, latent infections in their host. Spontaneous reactivation of herpesviruses is often asymptomatic or clinically manageable in healthy individuals, but reactivation events in immunocompromised or immunosuppressed individuals can lead to severe morbidity and mortality. Moreover, herpesvirus infections have been associated with multiple proliferative cardiovascular and post-transplant diseases. Herpesviruses encode viral G protein-coupled receptors (vGPCRs) that alter the host cell by hijacking cellular pathways and play important roles in the viral life cycle and these different disease settings. In this review, we discuss the pharmacological and signaling properties of these vGPCRs, their role in the viral life cycle, and their contribution in different diseases. Because of their prominent role, vGPCRs have emerged as promising drug targets, and the potential of vGPCR-targeting therapeutics is being explored. Overall, these vGPCRs can be considered as attractive targets moving forward in the development of antiviral, cancer, and/or cardiovascular disease treatments. SIGNIFICANCE STATEMENT: In the last decade, herpesvirus-encoded G protein-coupled receptors (GPCRs) have emerged as interesting drug targets with the growing understanding of their critical role in the viral life cycle and in different disease settings. This review presents the pharmacological properties of these viral receptors, their role in the viral life cycle and different diseases, and the emergence of therapeutics targeting viral GPCRs.
疱疹病毒是普遍存在的病原体，可在其宿主中建立终身潜伏感染。在健康个体中，疱疹病毒的自发激活通常无症状或在临床上易于控制，但免疫功能低下或免疫抑制个体中的激活事件可导致严重的发病率和死亡率。此外，疱疹病毒感染与多种增殖性心血管疾病和移植后疾病有关。疱疹病毒编码病毒G蛋白偶联受体（vGPCR），这些受体通过劫持细胞途径改变宿主细胞，并在病毒生命周期和这些不同的疾病环境中发挥重要作用。在本综述中，我们讨论了这些vGPCR的药理学和信号特性、它们在病毒生命周期中的作用以及它们在不同疾病中的贡献。由于其突出作用，vGPCR已成为有前景的药物靶点，并且正在探索靶向vGPCR的治疗方法的潜力。总体而言，在抗病毒、癌症和/或心血管疾病治疗的发展中，这些vGPCR可被视为有吸引力的靶点。意义声明：在过去十年中，随着对疱疹病毒编码的G蛋白偶联受体（GPCR）在病毒生命周期和不同疾病环境中的关键作用的日益了解，它们已成为有趣的药物靶点。本综述介绍了这些病毒受体的药理学特性、它们在病毒生命周期和不同疾病中的作用，以及靶向病毒GPCR的治疗方法的出现。
