Dsouza Lara, Yang Zhilong
Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
J Med Virol. 2025 Aug;97(8):e70563. doi: 10.1002/jmv.70563.
Nucleotides are the building blocks of DNA and RNA. They also play essential roles in various other biological processes, including protein glycosylation, ribosome biogenesis, and cytoskeletal function. The significance of the regulation of nucleotide metabolism has recently gained more attention in many physiological and pathological contexts, including viral infections that often reprogram host cell metabolism to support viral replication. However, whilst nucleotides have long been known to be important for viral nucleic acid synthesis, the molecular mechanisms undertaken by viruses to regulate nucleotide synthesis are only beginning to be understood. In this review, we present a comprehensive analysis of nucleotide regulation by upstream growth factor signaling mechanisms in various families of RNA and DNA viruses, such as herpesviruses, poxviruses, influenza viruses, and coronaviruses. We place a primary emphasis on discussing the signaling pathways as the regulatory mechanisms and highlight the gaps in understanding the mechanistic details. We underscore recent research that investigates the roles of different viral factors in modulating nucleotide metabolism in the infections of DNA and RNA viruses. Finally, we discuss the emerging area of inquiry that explores the relationship between nucleotide metabolism and immune regulation. A thorough understanding of how nucleotides are regulated during viral infections is essential for developing novel effective therapeutic strategies against these viruses.
核苷酸是DNA和RNA的组成成分。它们在各种其他生物过程中也发挥着重要作用，包括蛋白质糖基化、核糖体生物合成和细胞骨架功能。核苷酸代谢调控的重要性最近在许多生理和病理情况下受到了更多关注，包括病毒感染，病毒感染常常会重新编程宿主细胞代谢以支持病毒复制。然而，尽管长期以来人们都知道核苷酸对病毒核酸合成很重要，但病毒调节核苷酸合成所采用的分子机制才刚刚开始被理解。在这篇综述中，我们全面分析了RNA和DNA病毒各家族中上游生长因子信号传导机制对核苷酸的调控，如疱疹病毒、痘病毒、流感病毒和冠状病毒。我们主要着重于讨论作为调控机制的信号通路，并突出在理解机制细节方面存在的差距。我们强调了最近关于不同病毒因子在DNA和RNA病毒感染中调节核苷酸代谢作用的研究。最后，我们讨论了探索核苷酸代谢与免疫调节之间关系的新兴研究领域。深入了解病毒感染期间核苷酸是如何被调控的，对于开发针对这些病毒的新型有效治疗策略至关重要。
