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The role of the DE and EF loop of BKPyV VP1 in the serological cross-reactivity between subtypes

dc.contributor.authorHejtmánková, Alžběta
dc.contributor.authorCaisová, Helena
dc.contributor.authorTomanová, Tereza
dc.contributor.authorŠpanielová, Hana
dc.date.accessioned2023-06-06T08:03:53Z
dc.date.available2023-06-06T08:03:53Z
dc.date.issued2023
dc.identifier.urihttps://hdl.handle.net/20.500.14178/1938
dc.description.abstractBK virus (BKPyV) is a causative agent of BKPyV-associated nephropathy and graft rejections in kidney transplant patients. It establishes persistent infection in the kidneys, which can lead to reactivation in an immunosuppressed state or transmission to kidney recipients. Complications in the case of donor-derived infections can be caused by differences between the four known BKPyV subtypes, as prior infection with one subtype does not guarantee protection against de novo infection with other subtypes. The recipient and donor pretransplant serotyping is not routinely performed since simple ELISA tests employing antigens derived from the major viral capsid protein 1 (VP1) are hindered by the high cross-reactivity of anti-VP1 antibodies against all subtypes. Identifying subtype-specific epitopes in VP1 could lead to the design of specific antigens and the improvement of serodiagnostics for kidney transplantation. We aimed to study the surface residues responsible for the interactions with the subtype-specific antibodies by focusing on the DE and EF loops of VP1, which have only a small number of distinct amino acid differences between the most common subtypes, BKPyV-I and BKPyV-IV. We designed two mutant virus-like particles (VLPs): we introduced BKPyV-I characteristic amino acid residues (either H139N in the DE loop or D175E and I178V changes in the EF loop) into the base sequence of a BKPyV-IV VP1. This way, we created BKPyV-IV mutant VLPs with the sequence of either the BKPyV-I DE loop or the BKPyV-I EF loop. These mutants were then used as competing antigens in an antigen competition assay with a panel of patient sera, and changes in antibody reactivity were assessed by ELISA. We found that the changes introduced into the BKPyV-IV VP1 EF loop restrict antibody recognition in most samples and that converting the BKPyV-IV DE loop into its BKPyV-I equivalent attracts anti-VP1 BKPyV-I anti-bodies. Although our results did not lead to the discovery of a subtype-specific epitope on the VP1, they sug-gested that the arrangement of the EF loop in VP1 might dictate the mode of interaction between virus and anti-VP1 antibodies in general and that the interactions between the antibodies and the viral capsid might be very complex. Consequently, an antigen competition assay as an assay to distinguish between BKPyV serotypes might prove difficult to interpret.en
dc.language.isoen
dc.relation.urlhttps://doi.org/10.1016/j.virusres.2022.199031
dc.rightsCreative Commons Uveďte původ-Neužívejte dílo komerčně-Nezpracovávejte 4.0 Internationalcs
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivativeWorks 4.0 Internationalen
dc.titleThe role of the DE and EF loop of BKPyV VP1 in the serological cross-reactivity between subtypesen
dcterms.accessRightsopenAccess
dcterms.licensehttps://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
dc.date.updated2023-11-07T08:13:52Z
dc.subject.keywordpolyomavirus BKen
dc.subject.keywordBKPyVen
dc.subject.keywordBKPyV serostatusen
dc.subject.keywordBKPyV virus serologyen
dc.subject.keywordkidney transplantationen
dc.subject.keywordvirus-like particlesen
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/GAUK/GAUK1294120
dc.relation.fundingReferenceinfo:eu-repo/grantAgreement/UK/SVV/SVV260568
dc.date.embargoStartDate2023-11-07
dc.type.obd73
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1016/j.virusres.2022.199031
dc.identifier.utWos000919657600001
dc.identifier.eidScopus2-s2.0-85145740835
dc.identifier.obd631935
dc.identifier.pubmed36587871
dc.subject.rivPrimary10000::10600::10607
dcterms.isPartOf.nameVirus Research
dcterms.isPartOf.issn0168-1702
dcterms.isPartOf.journalYear2023
dcterms.isPartOf.journalVolume324
dcterms.isPartOf.journalIssue332
uk.faculty.primaryId115
uk.faculty.primaryNamePřírodovědecká fakultacs
uk.faculty.primaryNameFaculty of Scienceen
uk.department.primaryId1034
uk.department.primaryNameKatedra genetiky a mikrobiologiecs
uk.department.primaryNameDepartment of Genetics and Microbiologyen
dc.type.obdHierarchyCsČLÁNEK V ČASOPISU::článek v časopisu::původní článekcs
dc.type.obdHierarchyEnJOURNAL ARTICLE::journal article::original articleen
dc.type.obdHierarchyCode73::152::206en
uk.displayTitleThe role of the DE and EF loop of BKPyV VP1 in the serological cross-reactivity between subtypesen


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