All differential on the splicing front: Host alternative splicing alters the landscape of virus-host conflict

Alternative RNA splicing is a co-transcriptional process that richly increases proteome diversity, and is dynamically regulated based on cell species, lineage, and activation state. Virus infection in vertebrate hosts results in rapid host transcriptome-wide changes, and regulation of alternative splicing can direct a combinatorial effect on the host transcriptome. There has been a recent increase in genome-wide studies evaluating host alternative splicing during viral infection, which integrates well with prior knowledge on viral interactions with host splicing proteins. A critical challenge remains in linking how these individual events direct global changes, and whether alternative splicing is an overall favorable pathway for fending off or supporting viral infection. Here, we introduce the process of alternative splicing, discuss how to analyze splice regulation, and detail studies on genome-wide and splice factor changes during viral infection. We seek to highlight where the field can focus on moving forward, and how incorporation of a virus-host co-evolutionary perspective can benefit this burgeoning subject.