Antagonistic co-evolution throughout the herpesvirus life cycle

Herpesviruses are a widespread and diverse family of large double-stranded DNA viruses. Narrow host ranges maintained over long evolutionary times have fostered intimate host adaptations. However, such close virus-host associations inevitably invite conflict. Genetic conflict describes antagonistic interactions between two individuals that drive genetic changes to overcome said conflict. During the herpesvirus infectious cycle, genetic conflict-and specifically antagonistic co-evolution-can occur on multiple levels: between host and virus, between co-infecting viruses, or between genes within the same genome. This review highlights the many ways such conflict occurs and how it shapes herpesvirus evolution. Starting with attachment and entry, and continuing through gene expression, DNA metabolism, packaging, and egress, we examine how antagonistic interactions manifest at each stage of the viral life cycle. Latency and immunity receive special consideration as their inherent biology makes them focal points of sustained antagonism. Since genetic conflict is a major force in evolutionary ecology, we aim to emphasize its central role in herpesvirus biology and encourage future studies to explicitly consider the antagonistic forces shaping their evolution.