Ubiquitination dynamics in human tumour viruses: Viral infection, oncogenesis and antiviral therapy

The ubiquitin conjugation system is a critical regulator of cellular homeostasis and influences various cellular processes. Viruses, as obligate intracellular parasites, have evolved sophisticated strategies to utilise this system to enhance their survival, to either increase virus production or ensure the long-term survival of the latently infected host. Viruses from almost all families, including RNA and DNA viruses, are challenged by ubiquitin-mediated mechanisms at different stages of their life cycle and have evolved to exploit or bypass the host cell ubiquitination system for their own replication. In this review, we examine the diverse functions of the ubiquitin conjugation system during the different stages of viral infection, including viral entry, replication, gene expression, assembly and release. We discuss how human oncogenic viruses manipulate host ubiquitination pathways to maintain infection, evade immune responses and drive oncogenesis. Finally, we highlight new research aimed at uncovering the precise molecular interactions between oncoviruses and the host ubiquitination system, which will pave the way for the development of advanced therapeutic strategies to treat viral infections and cancer.