Prusinkiewicz Martin A, Mymryk Joe S
Department of Microbiology and Immunology, Western University, London, ON N6A 3K7, Canada.
Department of Otolaryngology, Head & Neck Surgery, Western University, London, ON N6A 3K7, Canada.
Pathogens. 2021 May 6;10(5):560. doi: 10.3390/pathogens10050560.
Viruses co-opt a multitude of host cell metabolic processes in order to meet the energy and substrate requirements for successful viral replication. However, due to their limited coding capacity, viruses must enact most, if not all, of these metabolic changes by influencing the function of available host cell regulatory proteins. Typically, certain viral proteins, some of which can function as viral oncoproteins, interact with these cellular regulatory proteins directly in order to effect changes in downstream metabolic pathways. This review highlights recent research into how four different DNA tumor viruses, namely human adenovirus, human papillomavirus, Epstein-Barr virus and Kaposi's associated-sarcoma herpesvirus, can influence host cell metabolism through their interactions with either MYC, p53 or the pRb/E2F complex. Interestingly, some of these host cell regulators can be activated or inhibited by the same virus, depending on which viral oncoprotein is interacting with the regulatory protein. This review highlights how MYC, p53 and pRb/E2F regulate host cell metabolism, followed by an outline of how each of these DNA tumor viruses control their activities. Understanding how DNA tumor viruses regulate metabolism through viral oncoproteins could assist in the discovery or repurposing of metabolic inhibitors for antiviral therapy or treatment of virus-dependent cancers.
病毒会利用多种宿主细胞代谢过程，以满足成功进行病毒复制所需的能量和底物需求。然而，由于其编码能力有限，病毒必须通过影响现有宿主细胞调节蛋白的功能来实现大部分（如果不是全部）这些代谢变化。通常，某些病毒蛋白，其中一些可作为病毒癌蛋白发挥作用，直接与这些细胞调节蛋白相互作用，从而影响下游代谢途径的变化。本综述重点介绍了近期关于四种不同的DNA肿瘤病毒，即人腺病毒、人乳头瘤病毒、爱泼斯坦-巴尔病毒和卡波西肉瘤相关疱疹病毒，如何通过与MYC、p53或pRb/E2F复合物相互作用来影响宿主细胞代谢的研究。有趣的是，取决于与调节蛋白相互作用的病毒癌蛋白，这些宿主细胞调节因子中的一些可被同一种病毒激活或抑制。本综述首先介绍了MYC、p53和pRb/E2F如何调节宿主细胞代谢，随后概述了每种DNA肿瘤病毒如何控制它们的活性。了解DNA肿瘤病毒如何通过病毒癌蛋白调节代谢，可能有助于发现或重新利用代谢抑制剂用于抗病毒治疗或治疗病毒相关癌症。
