Foot-and-mouth disease virus (FMDV), a member of theInfection of cells with most picornaviruses leads to a cytopathic effect (CPE) characterized by dramatic changes in cell shape and the production of large numbers of membrane vesicles within the cytoplasm. Early studies focused on the CPE produced by poliovirus (PV) and coxsackievirus (16,33,70) and revealed crystalline arrays of virus in the cytoplasm and viruses associated with, and contained within, membrane vesicles (7,10,43). The origin of vesicles induced by PV has been the subject of several studies with various conclusions. Highpressure freezing preparation for electron microscopy showed double-membrane vesicles in cells infected with PV (71). The vesicles are thought to be derived from the endoplasmic reticulum (ER), arising from either COPII-coated vesicles or autophagic vesicles (6,32,63,66,71,73,74). However, the presence of other organelle markers associated with PV vesicles, at later time points of infection, suggests that the ER is not the sole contributor of these membranes (66).In a previous publication (51), we reported that while footand-mouth disease virus (FMDV) induced the formation of membrane vesicles in infected cells, as observed in PV-infected cells, there were a number of differences between the effects observed with these two viruses. FMDV-induced vesicles predominantly had a single membrane and were not found in clusters as reported for PV. Further differences between PV and FMDV replication are seen in studies of virus sensitivity to the fungal metabolite, brefeldin A, which inhibits the function of Arf1-GTPase. Brefeldin A completely inhibits PV replication, whereas FMDV replication appears unaffected (15,22,30,48,51,58). Differences between PV and FMDV are also seen in some of the functions of the nonstructural proteins. Studies examining the effects of FMDV, and its nonstructural proteins, on the host-cell protein secretory pathway revealed that, unlike the PV 3A protein, FMDV 3A was unable to slow protein secretion (12,49). Interestingly, although both FMDV 2BC and PV 2BC are able to slow protein trafficking though the secretory pathway, they appear to act at different sites. PV 2BC is thought to slow the processing of secretory proteins at the Golgi body, whereas FMDV 2BC expression leads to retention of secretory proteins within the ER (2,19,49,50,64). Taken together, these observations indicate significant differences in the virus-host cell interactions of PV (an enterovirus) and FMDV (an aphthovirus).In contrast to the work on membrane vesicles, relatively little work has been reported on the effect of picornavirus infection on the cytoskeleton. However, it is becoming increasingly clear that many of these viruses use and modify the cytoskeleton for cell entry, replication, and egress. For example, Theiler's virus (a cardiovirus) has been reported to associate with intermediate filaments (55). PV has been reported to associate with the cytoskeleton and intermediate filaments (42,