Viral Reprogramming of Nucleotide Synthesis and Its Impact on Viral Infection

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.