on the host cell exocytic pathway because of the extensive use of intracellular membranes for assembly of replication complexes and viral particles. MHV utilizes the ER to generate membrane-associated replication complexes, termed double membrane vesicles, and to assemble progeny virus particles. We hypothesized that this extensive use of the ER induces the unfolded protein response. The UPR is a multifaceted signaling pathway that is triggered by perturbations in the normal ER environment (reviewed in Ref.2). The UPR emanates from the ER membrane and has the capacity to increase expression of ER resident chaperones and folding enzymes, to facilitate disposal of misfolded protein, to downregulate protein synthesis, to regulate production of membrane components necessary for expansion of the secretory pathway, and to regulate both cell cycle progression and cell death. Recently, investigators have reported that hepatitis C virus 5