Entry of poliovirus into cells does not require a low-pH step.
The requirement of a low-pH step during poliovirus entry was investigated by using the macrolide antibiotic bafilomycin A1, which is a powerful and selective inhibitor of the vacuolar proton-ATPases. Thus, viruses such as Semliki Forest virus and vesicular stomatitis virus that enter cells through endosomes and need their acidification, are potently inhibited by bafilomycin A1, whereas poliovirus infection is not affected by the antibiotic. The presence of lysosomotropic agents such as chloroquine, amantadine, dansylcadaverine, and monensin during poliovirus entry did not inhibit infection, further supporting the idea that poliovirus does not depend on a low-pH step to enter the cytoplasm. The effect of bafilomycin A1 on other members of the Picornaviridae family was also assayed. Encephalomyocarditis virus entry into HeLa cells was not affected by the macrolide antibiotic, whereas rhinovirus was sensitive. Coentry of toxins, such as alpha-sarcin, with viral particles was potently inhibited by bafilomycin A1, indicating that an active vacuolar proton-ATPase is necessary for the early membrane permeabilization (coentry of alpha-sarcin) induced by poliovirus to take place.
Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Spain.
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D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001345:Autoradiography; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018942:Macrolides; D008715:Methionine / Q000378:metabolism; D008954:Models, Biological; D008985:Monensin / Q000494:pharmacology; D017955:Poliovirus / Q000187:drug effects / Q000502:physiology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D012672:Semliki forest virus / Q000187:drug effects / Q000502:physiology*; D013462:Sulfur Radioisotopes; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects / Q000502:physiology; D014764:Viral Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects
D000900:Anti-Bacterial Agents; D018942:Macrolides; D013462:Sulfur Radioisotopes; D014764:Viral Proteins; D002738:Chloroquine; C040929:bafilomycin A1; D008985:Monensin; D008715:Methionine; D000547:Amantadine; D006180:Proton-Translocating ATPases; C008542:monodansylcadaverine; D002103:Cadaverine