SECRETORY PATHWAY FUNCTION, BUT NOT CYTOSKELETAL INTEGRITY, IS REQUIRED IN POLIOVIRUS INFECTION

We examined the importance of two interactions between poliovirus and its host cell: the putative association between viral proteins and a r earranged intermediate filament (IF) network and the apparent requirem ent for functional vesicle budding machinery within the host-cell secr etory pathway. Poliovirus capsid proteins appeared to associate with r eorganized IF proteins during infection. Treatment of cells with cytoc halasin D and nocodazole in combination disrupted normal cytoskeletal organization and prevented the poliovirus-induced redistribution of IF proteins to a juxtanuclear location. However, this treatment had no e ffect on viral yields from single-cycle infections, indicating that ne ither cytoskeletal integrity nor a specific poliovirus-induced rearran gement of IF proteins is required in the poliovirus life cycle. In con trast, we report that the inhibition of poliovirus replication by bref eldin A (BFA), an inhibitor of secretory membrane traffic, is specific to the host cell. Polioviral yields were not affected by BFA in two B FA-resistant cell lines, demonstrating that BFA targets a host protein or process required by poliovirus. No BFA-resistant virus was detecte d in these experiments, further supporting the hypothesis that poliovi rus replication requires secretory pathway function, perhaps for the g eneration of vesicles on which viral RNA replication complexes are ass embled.