Host Genetic Regulation of Stem Cell–Virus Interactions in Human Health

The interactions between human viruses and human stem cells may differ from those with differentiated cells. These differences may arise through heterogeneous intercellular mechanisms and responses to specific infectious agents, resulting in different phenotypes that affect human pathophysiology. Understanding and exploiting such differences could have clinical and translational potential. Here, we discuss the various mechanistic interactions between stem cells and viruses related to entry mechanisms, replication dynamics, and immunomodulation. In doing so, we critically assess proposed models and hypotheses about how viruses manipulate stem cell biology, while also providing new paradigms for stem cell biology and therapeutic interventions. We highlight recent discoveries on the dual role of viruses in oncogenesis and oncolysis. In parallel, we explore similarities between stem cells and complex viruses-such as giant viruses and jumbo phages-to propose novel perspectives on viral adaptability and pathogenesis. We examine both established mechanisms and emerging viral phenomena to encourage further research and debate on the clinical implications of viral interactions with stem cells.