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Glucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infection

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dc.creatorRoyle, Jamiespa
dc.creatorRamírez Santana, Heily Carolinaspa
dc.creatorAkpunarlieva, Snezhanaspa
dc.creatorDonald, Claire Lspa
dc.creatorGestuveo, Rommel Jspa
dc.creatorAnaya, Juan-Manuelspa
dc.date.accessioned2020-08-19T14:43:51Z
dc.date.available2020-08-19T14:43:51Z
dc.date.created2019-12-01spa
dc.description.abstractZika virus (ZIKV) is a member of the Flaviviridae family and was until recently a relatively obscure tropical disease. Subsequently, ZIKV has been shown to be the causative agent of fetal abnormalities and Guillain-Barré syndrome in outbreaks across the Americas and so efforts towards delineating important factors in the viral lifecycle have increased. Combining protein pull-down with mass spectrometry, it was found that ZIKV envelope (Env) interacts with the endoplasmic reticulum (ER) resident chaperone, glucose regulated protein 78 (GRP78) in A549 cells. Flaviviruses such as Japanese encephalitis virus and dengue virus are known to co-opt ER resident proteins and members of the unfolded protein response, including GRP78, to enhance viral infectivity and propagation. The role these proteins play during the ZIKV lifecycle has yet to be elucidated. To determine the importance of this interaction during ZIKV infection, A549 cells were treated with GRP78-specific siRNAs prior to infection with a NanoLuc expressing reporter virus or a wild-type virus. Depletion of GRP78 significantly reduced both virus luciferase readings and viral titres, indicating that GRP78 is necessary for efficient infection of mammalian cell culture. In contrast, inhibition of GRP78 with small molecule inhibitors did not reduce ZIKV infection. Interestingly, immunofluorescence of ZIKV infected cells reveal that GRP78 re-localises following infection and co-localises with Env. Depletion of GRP78 abrogated localisation of viral replication factories. Further experiments have shown that GRP78 is important for infection post entry and replication, and that putative GRP78 interactions partners are also required during infection.eng
dc.format.mimetypeapplication/pdf
dc.identifier.doihttps://doi.org/10.1099/acmi.imav2019.po0021
dc.identifier.issnEISSN: 2516-8290
dc.identifier.urihttps://repository.urosario.edu.co/handle/10336/27782
dc.language.isoengspa
dc.publisherMicrobiology Societyspa
dc.relation.citationIssueNo. 10
dc.relation.citationStartPage12050524
dc.relation.citationTitleAccess Microbiology
dc.relation.citationVolumeVol. 1
dc.relation.ispartofAccess Microbiology, EISSN: 2516-8290, Vol.1, No.10 (2019); pp. 12050524spa
dc.relation.urihttps://www.microbiologyresearch.org/content/journal/acmi/10.1099/acmi.imav2019.po0021spa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.sourceAccess Microbiologyspa
dc.source.instnameinstname:Universidad del Rosario
dc.source.reponamereponame:Repositorio Institucional EdocUR
dc.subject.keywordZika virusspa
dc.subject.keywordZIKV infectionspa
dc.subject.keywordGuillain-Barré syndromespa
dc.subject.keywordGRP78spa
dc.subject.keywordProteomicsspa
dc.subject.keywordVirus–cell interactionsspa
dc.titleGlucose regulated protein 78 (GRP78) interacts with Zika virus envelope and is required for a productive infectionspa
dc.title.TranslatedTitleLa proteína 78 regulada por glucosa (GRP78) interactúa con la envoltura del virus del Zika y es necesaria para una infección productivaspa
dc.typearticleeng
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersion
dc.type.spaArtículospa
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