We explore how viral infection reshapes the gene expression landscape of mammalian cells. This encompasses viral repurposing and altering of cellular gene regulation machinery to promote virus replication, as well as cellular responses to viral invasion. We primarily study these events using gammaherpesviruses such as Kaposi’s sarcoma-associated herpesvirus, which is a major cause of AIDS-associated cancers. Our research is revealing how virus-host interactions can have unexpected consequences for gene expression that provide insight into both virus and host biology.