Inhibitors of COP-mediated transport and cholera toxin action inhibit simian virus 40 infection.
Simian virus 40 (SV40) is a nonenveloped virus that has been shown to pass from surface caveolae to the endoplasmic reticulum in an apparently novel infectious entry pathway. We now show that the initial entry step is blocked by brefeldin A and by incubation at 20 degrees C. Subsequent to the entry step, the virus reaches a domain of the rough endoplasmic reticulum by an unknown pathway. This intracellular trafficking pathway is also brefeldin A sensitive. Infection is strongly inhibited by expression of GTP-restricted ADP-ribosylation factor 1 (Arf1) and Sar1 mutants and by microinjection of antibodies to betaCOP. In addition, we demonstrate a potent inhibition of SV40 infection by the dipeptide N-benzoyl-oxycarbonyl-Gly-Phe-amide, which also inhibits late events in cholera toxin action. Our results identify novel inhibitors of SV40 infection and show that SV40 requires COPI- and COPII-dependent transport steps for successful infection.
Richards
Ayanthi A
AA
Institute for Molecular Bioscience, Center for Microscopy and Microanalysis, Queensland 4072, Australia.
Stang
Espen
E
Pepperkok
Rainer
R
Parton
Robert G
RG
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D020126:Brefeldin A / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D002522:Chlorocebus aethiops; D002772:Cholera Toxin / Q000037:antagonists & inhibitors*; D004151:Dipeptides / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D027601:Polyomavirus Infections / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013539:Simian virus 40 / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013696:Temperature; D014709:Vero Cells; D033921:Vesicular Transport Proteins
D000998:Antiviral Agents; D002352:Carrier Proteins; D004151:Dipeptides; C436144:LLID-114769 protein, human; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; D020126:Brefeldin A; C066375:carbobenzoxyglycylphenylalanine amide; D002772:Cholera Toxin; D020823:ADP-Ribosylation Factor 1; D020559:Monomeric GTP-Binding Proteins; C077395:SAR1 protein, S cerevisiae