Protein Kinase C subtype delta interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation

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dc.contributor.authorCarey, Brian D.en
dc.contributor.authorAkhrymuk, Ivan V.en
dc.contributor.authorDahal, Bibhaen
dc.contributor.authorPinkham, Chelsea L.en
dc.contributor.authorBracci, Nicole R.en
dc.contributor.authorFinstuen-Magro, Sarahen
dc.contributor.authorLin, Shih-Chaoen
dc.contributor.authorLehman, Caitlin W.en
dc.contributor.authorSokoloski, Kevin J.en
dc.contributor.authorKehn-Hall, Kyleneen
dc.contributor.departmentBiomedical Sciences and Pathobiologyen
dc.date.accessioned2021-09-27T14:47:27Zen
dc.date.available2021-09-27T14:47:27Zen
dc.date.issued2020-03-01en
dc.date.updated2021-09-27T14:47:23Zen
dc.description.abstractProtein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Phosphorylation site prediction software suggests that Protein Kinase C (PKC) is responsible for phosphorylation of VEEV capsid. VEEV capsid co-immunoprecipitated with PKCδ, but not other PKC isoforms and siRNA knockdown of PKCδ caused a decrease in viral replication. Furthermore, knockdown of PKCδ by siRNA decreased capsid phosphorylation. A virus with capsid phosphorylation sites mutated to alanine (VEEV CPD) displayed a lower genomic copy to pfu ratio than the parental virus; suggesting more efficient viral assembly and more infectious particles being released. RNA:capsid binding was significantly increased in the mutant virus, confirming these results. Finally, VEEV CPD is attenuated in a mouse model of infection, with mice showing increased survival and decreased clinical signs as compared to mice infected with the parental virus. Collectively our data support a model in which PKCδ mediated capsid phosphorylation regulates viral RNA binding and assembly, significantly impacting viral pathogenesis.en
dc.description.versionPublished versionen
dc.format.extent25 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e1008282 (Article number)en
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1008282en
dc.identifier.eissn1553-7374en
dc.identifier.issn1553-7366en
dc.identifier.issue3en
dc.identifier.orcidKehn-Hall, Kylene [0000-0001-8036-7213]en
dc.identifier.otherPPATHOGENS-D-19-01010 (PII)en
dc.identifier.pmid32150585en
dc.identifier.urihttp://hdl.handle.net/10919/105082en
dc.identifier.volume16en
dc.language.isoenen
dc.publisherPLoSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000523706200045&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectLife Sciences & Biomedicineen
dc.subjectMicrobiologyen
dc.subjectParasitologyen
dc.subjectVirologyen
dc.subjectREPLICATIONen
dc.subjectACTIVATIONen
dc.subjectINFECTIONen
dc.subjectCELLSen
dc.subjectPHOSPHOPROTEINen
dc.subjectALPHAVIRUSESen
dc.subjectATTENUATIONen
dc.subjectINHIBITIONen
dc.subjectEXPRESSIONen
dc.subjectSEQUENCESen
dc.subject0605 Microbiologyen
dc.subject1107 Immunologyen
dc.subject1108 Medical Microbiologyen
dc.subjectVirologyen
dc.subject.meshAnimalsen
dc.subject.meshMice, Inbred C3Hen
dc.subject.meshHorsesen
dc.subject.meshMiceen
dc.subject.meshEncephalitis Virus, Venezuelan Equineen
dc.subject.meshCapsiden
dc.subject.meshEncephalomyelitis, Venezuelan Equineen
dc.subject.meshCapsid Proteinsen
dc.subject.meshRNA, Viralen
dc.subject.meshProtein Bindingen
dc.subject.meshPhosphorylationen
dc.subject.meshFemaleen
dc.subject.meshProtein Kinase C-deltaen
dc.subject.meshHost-Pathogen Interactionsen
dc.titleProtein Kinase C subtype delta interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylationen
dc.title.serialPLOS Pathogensen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2019-12-13en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Veterinary Medicineen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/Biomedical Sciences and Pathobiologyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Veterinary Medicine/CVM T&R Facultyen

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