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2022-04-07Zeitschriftenartikel
A Conserved Cysteine Residue in Coxsackievirus B3 Protein 3A with Implication for Elevated Virulence
dc.contributor.authorVoss, Martin
dc.contributor.authorPinkert, Sandra
dc.contributor.authorKespohl, Meike
dc.contributor.authorGimber, Niclas
dc.contributor.authorKlingel, Karin
dc.contributor.authorSchmoranzer, Jan
dc.contributor.authorLaue, Michael
dc.contributor.authorGaida, Matthias
dc.contributor.authorKloetzel, Peter-Michael
dc.contributor.authorBeling, Antje
dc.date.accessioned2024-08-29T14:35:12Z
dc.date.available2024-08-29T14:35:12Z
dc.date.issued2022-04-07none
dc.identifier.other10.3390/v14040769
dc.identifier.urihttp://edoc.rki.de/176904/12043
dc.description.abstractEnteroviruses (EV) are implicated in an extensive range of clinical manifestations, such as pancreatic failure, cardiovascular disease, hepatitis, and meningoencephalitis. We recently reported on the biochemical properties of the highly conserved cysteine residue at position 38 (C38) of enteroviral protein 3A and demonstrated a C38-mediated homodimerization of the Coxsackievirus B3 protein 3A (CVB3-3A) that resulted in its profound stabilization. Here, we show that residue C38 of protein 3A supports the replication of CVB3, a clinically relevant member of the enterovirus genus. The infection of HeLa cells with protein 3A cysteine 38 to alanine mutants (C38A) attenuates virus replication, resulting in comparably lower virus particle formation. Consistently, in a mouse infection model, the enhanced virus propagation of CVB3-3A wt in comparison to the CVB3-3A[C38A] mutant was confirmed and found to promote severe liver tissue damage. In contrast, infection with the CVB3-3A[C38A] mutant mitigated hepatic tissue injury and ameliorated the signs of systemic inflammatory responses, such as hypoglycemia and hypothermia. Based on these data and our previous report on the C38-mediated stabilization of the CVB3-3A protein, we conclude that the highly conserved amino acid C38 in protein 3A enhances the virulence of CVB3.eng
dc.language.isoengnone
dc.publisherRobert Koch-Institut
dc.rights(CC BY 3.0 DE) Namensnennung 3.0 Deutschlandger
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/de/
dc.subjectenteroviruseng
dc.subjectcoxsackievirusB3eng
dc.subjectinfectioneng
dc.subjectanimal modeleng
dc.subjectvirulence regulationeng
dc.subject.ddc610 Medizin und Gesundheitnone
dc.titleA Conserved Cysteine Residue in Coxsackievirus B3 Protein 3A with Implication for Elevated Virulencenone
dc.typearticle
dc.identifier.urnurn:nbn:de:0257-176904/12043-6
dc.type.versionpublishedVersionnone
local.edoc.container-titlevirusesnone
local.edoc.container-issn1999-4915none
local.edoc.pages15none
local.edoc.type-nameZeitschriftenartikel
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-urlhttps://www.mdpi.com/journal/virusesnone
local.edoc.container-publisher-nameMDPInone
local.edoc.container-volume14none
local.edoc.container-issue4none
local.edoc.container-reportyear2022none
dc.description.versionPeer Reviewednone

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