Rift Valley fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley fever virus production

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dc.contributor.authorBracci, Nicoleen
dc.contributor.authorde la Fuente, Cynthiaen
dc.contributor.authorSaleem, Saharen
dc.contributor.authorPinkham, Chelseaen
dc.contributor.authorNarayanan, Aarthien
dc.contributor.authorGarcia-Sastre, Adolfoen
dc.contributor.authorBalaraman, Velmuruganen
dc.contributor.authorRicht, Juergen A.en
dc.contributor.authorWilson, Williamen
dc.contributor.authorKehn-Hall, Kyleneen
dc.date.accessioned2023-05-31T13:29:09Zen
dc.date.available2023-05-31T13:29:09Zen
dc.date.issued2022-02en
dc.description.abstractRift Valley fever virus (RVFV) is an arbovirus that was first reported in the Rift Valley of Kenya which causes significant disease in humans and livestock. RVFV is a tri-segmented, negative-sense RNA virus consisting of a L, M, and S segments with the M segment encoding the glycoproteins Gn and Gc. Host factors that interact with Gn are largely unknown. To this end, two viruses containing an epitope tag (V5) on the Gn protein in position 105 or 229 (V5Gn105 and V5Gn229) were generated using the RVFV MP-12 vaccine strain as a backbone. The V5-tag insertion minimally impacted Gn functionality as measured by replication kinetics, Gn localization, and antibody neutralization assays. A proteomics-based approach was used to identify novel Gn-binding host proteins, including the E3 ubiquitin-protein ligase, UBR4. Depletion of UBR4 resulted in a significant decrease in RVFV titers and a reduction in viral RNA production.en
dc.description.adminPublic domain – authored by a U.S. government employeeen
dc.description.notesFunding for this study was provided through grants from NBAF Transition Funds from the State of Kansas (JAR), the Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD), under grant number HSHQDC 16-A-B0006 (JAR), and the MCB Core of the Center on Emerging and Zoonotic Infectious Diseases (CEZID), the National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health under award number P20GM130448 (JAR). WCW is supported by the USDA, Agricultural Research Service.en
dc.description.sponsorshipNBAF Transition Funds from the State of Kansas; Department of Homeland Security Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD) [HSHQDC 16-A-B0006]; MCB Core of the Center on Emerging and Zoonotic Infectious Diseases (CEZID); National Institute of General Medical Sciences (NIGMS) of the National Institutes of Health [P20GM130448]; USDA, Agricultural Research Serviceen
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.virol.2021.12.010en
dc.identifier.eissn1089-862Xen
dc.identifier.issn0042-6822en
dc.identifier.pmid35032865en
dc.identifier.urihttp://hdl.handle.net/10919/115268en
dc.identifier.volume567en
dc.language.isoenen
dc.publisherAcademic Pressen
dc.rightsPublic Domain (U.S.)en
dc.rights.urihttp://creativecommons.org/publicdomain/mark/1.0/en
dc.subjectRift valley fever virusen
dc.subjectGlycoproteinsen
dc.subjectUBR4en
dc.subjectGnen
dc.titleRift Valley fever virus Gn V5-epitope tagged virus enables identification of UBR4 as a Gn interacting protein that facilitates Rift Valley fever virus productionen
dc.title.serialVirologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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