Abstract
Picornaviruses are positive-stranded RNA viruses of significant disease burden and ubiquitous global reach. Microscopic examination of picornavirus-infected cells has long revealed a drastic reordering of intracellular membranes. Through a confluence of candidate-based approaches and genomic and proteomic screens, the past decade has seen great leaps in understanding how picornaviruses usurp intracellular membranes for their own replication. The growing cast of assembled characters allows for a rich plot in the upcoming years. With their widespread genomic divergence, the number of potential mechanisms for RNA virus vesicogenesis for driving membrane formation and lipid synthesis required for viral replication is broad, but the overall story arch remains surprisingly recognizable. This chapter reviews the major discoveries associating picornavirus pathogenic interactions with the secretory system and highlights important questions and opportunities for future study.