title: Entry of feline calicivirus is dependent on clathrin-mediated endocytosis and acidification in endosomes.
abstract: Feline calicivirus is a major causative agent of respiratory disease in cats. It is also one of the few cultivatable members of Caliciviridae. We have examined the entry process of feline calicivirus (FCV). An earlier study demonstrated that acidification in endosomes may be required. We have confirmed this observation and expanded upon it, demonstrating, using drugs to inhibit the various endocytic pathways and dominant-negative mutants, that FCV infects cells via clathrin-mediated endocytosis. We have also observed that FCV permeabilizes cell membranes early during infection to allow the co-entry of toxins such as alpha-sarcin. Inhibitors of endosome acidification such as chloroquine and bafilomycin A1 blocked this permeabilization event, demonstrating that acidification is required for uncoating of the genome and access to the cytoplasm.
authors.affiliation: Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. ads35@mole.bio.cam.ac.uk
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Stuart
authors.forename: T David K
authors.initials: TD
authors.lastname: Brown
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D017927:Calicivirus, Feline / Q000502:physiology*; D002415:Cats; D002462:Cell Membrane / Q000821:virology; D002738:Chloroquine / Q000494:pharmacology; D002966:Clathrin / Q000378:metabolism*; D003593:Cytoplasm / Q000821:virology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D004722:Endoribonucleases / Q000494:pharmacology; D011992:Endosomes / Q000378:metabolism / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000494:pharmacology; D005799:Genes, Dominant; D016679:Genome, Viral; D018942:Macrolides / Q000494:pharmacology; D010539:Permeability / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D011991:Receptors, Virus / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000143:Acids; D000962:Antimalarials; D002966:Clathrin; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D018942:Macrolides; D011500:Protein Synthesis Inhibitors; D012367:RNA, Viral; D011991:Receptors, Virus; C014801:alpha-sarcin; D002738:Chloroquine; C040929:bafilomycin A1; D004722:Endoribonucleases; D006180:Proton-Translocating ATPases; D020696:rab5 GTP-Binding Proteins