Abstract
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.
MeSH Terms
Amantadine/pharmacology
Animals
Anti-Bacterial Agents/pharmacology
Autoradiography
Cadaverine/analogs & derivatives,pharmacology
Cell Line
Chloroquine/pharmacology
Electrophoresis, Polyacrylamide Gel
HeLa Cells
Humans
Hydrogen-Ion Concentration
Macrolides
Methionine/metabolism
Models, Biological
Monensin/pharmacology
Poliovirus/drug effects,physiology
Proton-Translocating ATPases/antagonists & inhibitors
Semliki forest virus/drug effects,physiology
Sulfur Radioisotopes
Vesicular stomatitis Indiana virus/drug effects,physiology
Viral Proteins/biosynthesis,isolation & purification
Virus Replication/drug effects
Chemicals
Anti-Bacterial Agents
Macrolides
Sulfur Radioisotopes
Viral Proteins
Chloroquine
bafilomycin A1
Monensin
Methionine
Amantadine
Proton-Translocating ATPases
monodansylcadaverine
Cadaverine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pérez L
Centro de Biología Molecular Severo Ochoa (Consejo Superior de Investigaciones Cientificas-Universidad Autónoma de Madrid), Universidad Autónoma de Madrid, Spain.
Carrasco L
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