Picornavirus Modification of a Host mRNA Decay Protein

ABSTRACT Due to the limited coding capacity of picornavirus genomic RNAs, host RNA binding proteins play essential roles dur-ing viral translation andRNA replication.Herewe describe experiments suggesting that AUF1, a host RNAbinding protein involved in mRNAdecay, plays a role in the infectious cycle of picornaviruses such as poliovirus andhuman rhinovirus.We observed cleavage of AUF1during poliovirus or human rhinovirus infection, aswell as interaction of this proteinwith the 5=noncoding regions of these viral genomes. Additionally, the picornavirus proteinase 3CD, encoded by poliovirus or human rhinovirus genomic RNAs, was shown to cleave all four isoforms of recombinant AUF1 at a specific N-terminal site in vitro. Finally, endogenous AUF1 was found to relocalize from the nucleus to the cytoplasm in poliovirus-infected HeLa cells to sites adjacent to (but distinct from) putative viral RNA replication complexes. IMPORTANCE This study derives its significance from reporting how picornaviruses like poliovirus and human rhinovirus pro-teolytically cleave a key player (AUF1) in host mRNA decay pathways during viral infection. Beyond cleavage of AUF1 by the ma-jor viral proteinase encoded in picornavirus genomes, infection by poliovirus results in the relocalization of this host cell RNA binding protein from the nucleus to the cytoplasm. The alteration of both the physical state of AUF1 and its cellular location illuminates how small RNA viruses manipulate the activities of host cell RNA binding proteins to ensure a faithful intracellula