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 rearranged intermediate filament (IF) network and the apparent requirement for functional vesicle budding machinery within the host-cell secretory pathway. Poliovirus capsid proteins appeared to associate with reorganized IF proteins during infection. Treatment of cells with cytochalasin 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 effect on viral yields from single-cycle infections, indicating that neither cytoskeletal integrity nor a specific poliovirus-induced rearrangement of IF proteins is required in the poliovirus life cycle. In contrast, we report that the inhibition of poliovirus replication by brefeldin A (BFA), an inhibitor of secretory membrane traffic, is specific to the host cell. Polioviral yields were not affected by BFA in two BFA-resistant cell lines, demonstrating that BFA targets a host protein or process required by poliovirus. No BFA-resistant virus was detected in these experiments, further supporting the hypothesis that poliovirus replication requires secretory pathway function, perhaps for the generation of vesicles on which viral RNA replication complexes are assembled.
Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder.
J
J
Doedens
L A
LA
Maynell
M W
MW
Klymkowsky
K
K
Kirkegaard
D000818:Animals; D000956:Antigens, Viral / Q000302:isolation & purification; D000998:Antiviral Agents / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A; D002478:Cells, Cultured; D003517:Cyclopentanes / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007382:Intermediate Filaments / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects / Q000254:growth & development*; D013045:Species Specificity; D014779:Virus Replication / Q000187:drug effects
D000956:Antigens, Viral; D000998:Antiviral Agents; D003517:Cyclopentanes; D020126:Brefeldin A; D015638:Cytochalasin D; D015739:Nocodazole