About: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

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About: Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner
Creator	Rottier, Peter Perlman, Stanley van Kuppeveld, Frank Burkard, Christine Wicht, Oliver Haagmans, Bart Pelkmans, Lucas de Haan, Cornelis Bosch, Berend Verheije, Monique van Kasteren, Sander
source	Medline; PMC
abstract	Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion.
has issue date	2014-11-06(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1004502
bibo:pmid	25375324
has license	cc-by
schema:url	https://doi.org/10.1371/journal.ppat.1004502
resource representing a document's title	Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner
has PubMed Central identifier	PMC4223067
has PubMed identifier	25375324
schema:publication	PLoS Pathog
resource representing a document's body	covid:PMC4223067#body_text
is schema:about of	named entity 'Coronavirus' named entity 'Proteolysis' named entity 'proteases' named entity 'low pH' named entity 'growth kinetics' named entity 'DMSO' named entity 'PLCP' named entity 'siRNAs' named entity 'centrifugation' named entity 'virus' named entity 'infection' named entity 'CAV2' named entity 'expression cassette' named entity 'CAV1' named entity 'N-terminal' named entity 'clathrin-mediated endocytosis' named entity 'MHV' named entity 'MHV' named entity 'Transfection' named entity 'lysosome' named entity 'ACTR3' named entity 'wild type' named entity 'RAB7a' named entity 'peptide' named entity 'MHV' named entity 'cell-cell' named entity 'wild type' named entity 'FIPV' named entity 'lysosomal' named entity 'FACS' named entity 'gene' named entity 'murine' named entity 'Transfection' named entity 'cellular processes' named entity 'DMEM' named entity 'spike protein' named entity 'pathogens' named entity 'Qiagen' named entity 'actin cytoskeleton' named entity 'DYNC2H1' named entity 'cleavage site' named entity 'Endocytic' named entity 'cytoskeleton' named entity 'protein' named entity 'Leica' named entity 'G418' named entity 'FBS' named entity 'expression levels' named entity 'gene' named entity 'cleavage' named entity 'MHV' named entity 'MHV' named entity 'Murine' named entity 'HCoV-NL63' named entity 'transcription' named entity 'heptad repeat' named entity 'murine' named entity 'cell tropism' named entity 'dark orange' named entity 'lysosomes' named entity 'MHV' named entity 'luciferase' named entity 'sucrose' named entity 'MHV' named entity 'CHX' named entity 'hpi' named entity 'clathrin' named entity 'MHV' named entity 'siRNA' named entity 'expression levels' named entity 'lysosomes' named entity 'proteases'

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