Within- and between-host evolutionary effects on viral oncogenicity

Cancer-inducing viruses (oncogenic viruses) are linked to over 10% of cancer cases. Although the molecular details of viral oncogenesis are well-documented, the evolutionary mechanisms by which viruses have acquired oncogenic properties remain poorly understood. Here, we investigate the evolutionary conditions affecting viral oncogenicity across both within- and between-host scales using mathematical models of oncovirus-immune system interactions, conceptualized as an extended shared enemy-victim relationship. We begin by examining how oncogenic traits impact within-host viral dynamics, focusing on the transformation rate of infected cells into pre-cancerous states and the pre-cancerous cell proliferation rate. In various scenarios reflecting different within-host conditions, we then identify the transformation and proliferation rates that maximize within- and between-host viral fitness. We find that the transformation rate maximizing the viral load depends on the viral production rate, immunogenicity, and the immune-mediated elimination rate of pre-cancerous cells. We also identify conditions under which an intermediate proliferation rate minimizes within- and between-host viral fitness: in that scenario, a lower or higher proliferation rate leads to a higher viral load, providing a possible explanation for the diversity of oncogenic viruses. The analyses presented here provide insights into the evolutionary drivers affecting viral oncogenicity and highlight the complexity of oncogenic virus-immune system interactions.