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dc.contributor.authorPiccinotti, Silviaen_US
dc.contributor.authorWhelan, Sean P. J.en_US
dc.date.accessioned2016-10-11T20:27:28Z
dc.date.issued2016en_US
dc.identifier.citationPiccinotti, Silvia, and Sean P. J. Whelan. 2016. “Rabies Internalizes into Primary Peripheral Neurons via Clathrin Coated Pits and Requires Fusion at the Cell Body.” PLoS Pathogens 12 (7): e1005753. doi:10.1371/journal.ppat.1005753. http://dx.doi.org/10.1371/journal.ppat.1005753.en
dc.identifier.issn1553-7366en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29002625
dc.description.abstractThe single glycoprotein (G) of rabies virus (RABV) dictates all viral entry steps from receptor engagement to membrane fusion. To study the uptake of RABV into primary neuronal cells in culture, we generated a recombinant vesicular stomatitis virus in which the G protein was replaced with that of the neurotropic RABV CVS-11 strain (rVSV CVS G). Using microfluidic compartmentalized culture, we examined the uptake of single virions into the termini of primary neurons of the dorsal root ganglion and ventral spinal cord. By pharmacologically disrupting endocytosis at the distal neurites, we demonstrate that rVSV CVS G uptake and infection are dependent on dynamin. Imaging of single virion uptake with fluorescent endocytic markers further identifies endocytosis via clathrin-coated pits as the predominant internalization mechanism. Transmission electron micrographs also reveal the presence of viral particles in vesicular structures consistent with incompletely coated clathrin pits. This work extends our previous findings of clathrin-mediated uptake of RABV into epithelial cells to two neuronal subtypes involved in rabies infection in vivo. Chemical perturbation of endosomal acidification in the neurite or somal compartment further shows that establishment of infection requires pH-dependent fusion of virions at the cell body. These findings correlate infectivity to existing single particle evidence of long-range endosomal transport of RABV and clathrin dependent uptake at the plasma membrane.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1005753en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963122/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectCell Biologyen
dc.subjectCellular Typesen
dc.subjectAnimal Cellsen
dc.subjectNeuronsen
dc.subjectNeuroscienceen
dc.subjectCellular Neuroscienceen
dc.subjectNeuronal Dendritesen
dc.subjectNeuritesen
dc.subjectMicrobiologyen
dc.subjectVirologyen
dc.subjectViral Structureen
dc.subjectVirionsen
dc.subjectMotor Neuronsen
dc.subjectBiology and life sciencesen
dc.subjectOrganismsen
dc.subjectVirusesen
dc.subjectRNA virusesen
dc.subjectLyssavirusen
dc.subjectRabies Virusen
dc.subjectMedical Microbiologyen
dc.subjectMicrobial Pathogensen
dc.subjectViral Pathogensen
dc.subjectMedicine and Health Sciencesen
dc.subjectPathology and Laboratory Medicineen
dc.subjectPathogensen
dc.subjectCellular Structures and Organellesen
dc.subjectVesiclesen
dc.subjectEndosomesen
dc.subjectCell Physiologyen
dc.subjectCell Fusionen
dc.subjectCell Processesen
dc.subjectEndocytosisen
dc.subjectSecretory Pathwayen
dc.titleRabies Internalizes into Primary Peripheral Neurons via Clathrin Coated Pits and Requires Fusion at the Cell Bodyen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorPiccinotti, Silviaen_US
dc.date.available2016-10-11T20:27:28Z
dc.identifier.doi10.1371/journal.ppat.1005753*
dash.contributor.affiliatedPiccinotti, Silvia
dash.contributor.affiliatedWhelan, Sean


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