Our research focuses on how picornaviruses (including human rhinovirus, poliovirus, and coxsackievirus) regulate the expression and replication of their genomic RNAs in infected human cells. The limited coding capacity of picornavirus genomic RNAs results in a genetically-challenged RNA virus. As a result, picornaviruses have evolved to utilize host cell proteins in different steps of their intracellular, cytoplasmic replication cycles. Somewhat surprisingly, several proteins known or suspected to have roles in viral gene expression and RNA replication reside primarily in the nucleus of uninfected mammalian cells. Due to viral-specific alteration of protein trafficking between the cytoplasm and the nucleus of infected cells, such proteins become available for viral functions in the cytoplasm.