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dc.contributor.authorPantaleão, Simone Queiroz
dc.contributor.authorCamillo, Lívia de Moraes Bomediano
dc.contributor.authorNeves, Tainan Cerqueira
dc.contributor.authorMenezes, Isabela de Godoy
dc.contributor.authorStangherlin, Lucas Matheus
dc.contributor.authorBatista, Helena Beatriz de Carvalho Ruthner
dc.contributor.authorPoole, Emma
dc.contributor.authorNevels, Michael
dc.contributor.authorPhilot, Eric Alisson
dc.contributor.authorScott, Ana Ligia
dc.contributor.authorCarlan da Silva, Maria Cristina
dc.identifier.citationPantaleão , S Q , Camillo , L D M B , Neves , T C , Menezes , I D G , Stangherlin , L M , Batista , H B D C R , Poole , E , Nevels , M , Philot , E A , Scott , A L & Carlan da Silva , M C 2022 , ' Molecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptor ' , PLoS ONE , vol. 17 , no. 11 , e0277953 .
dc.identifier.otherPURE: 282343458
dc.identifier.otherPURE UUID: 9ca82890-2e04-4bbc-a51e-81cfc8a4b9b5
dc.identifier.otherRIS: urn:14EA79A533AF52DEE9F96DB51D3543B0
dc.identifier.otherORCID: /0000-0002-7115-407X/work/124078633
dc.identifier.otherScopus: 85142939325
dc.identifier.otherWOS: 000925006300069
dc.descriptionFunding: Funder 01: Grant number: 2020/08527-1 Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil (FAPESP) - Author: Maria Cristina Carlan da Silva - Maria Cristina Carlan Silva Funder 02: Grant number: 2020/07767-9 Fundação de Amparo a Pesquisa do Estado de São Paulo, Brazil (FAPESP) - Author: Tainan Cerqueira Neves - Neves, Tainan C. Funder 03: Grant number: 164052/2020-8 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) - Author: Simone Queiroz Pantaleão - Pantaleão, Simone Queiroz.en
dc.description.abstractThe human cytomegalovirus (HCMV) UL111A gene encodes several homologs of the cellular interleukin 10 (cIL-10). Alternative splicing in the UL111A region produces two relatively well-characterized transcripts designated cmvIL-10 (isoform A) and LAcmvIL-10 (isoform B). The cmvIL-10 protein is the best characterized, both structurally and functionally, and has many immunosuppressive activities similar to cIL-10, while LAcmvIL-10 has more restricted biological activities. Alternative splicing also results in five less studied UL111A transcripts encoding additional proteins homologous to cIL-10 (isoforms C to G). These transcripts were identified during productive HCMV infection of MRC-5 cells with the high passage laboratory adapted AD169 strain, and the structure and properties of the corresponding proteins are largely unknown. Moreover, it is unclear whether these protein isoforms are able to bind the cellular IL-10 receptor and induce signalling. In the present study, we investigated the expression spectrum of UL111A transcripts in fully permissive MRC-5 cells and semi permissive U251 cells infected with the low passage HCMV strain TB40E. We identified a new spliced transcript (H) expressed during productive infection. Using computational methods, we carried out molecular modelling studies on the three-dimensional structures of the HCMV IL-10 proteins encoded by the transcripts detected in our work (cmvIL-10 (A), LAcmvIL-10 (B), E, F and H) and on their interaction with the human IL-10 receptor (IL-10R1). The modelling predicts clear differences between the isoform structures. Furthermore, the in silico simulations (molecular dynamics simulation and normal-mode analyses) allowed us to evaluate regions that contain potential receptor binding sites in each isoform. The analyses demonstrate that the complexes between the isoforms and IL-10R1 present different types of molecular interactions and consequently different affinities and stabilities. The knowledge about structure and expression of specific viral IL-10 isoforms has implications for understanding of their properties and role in HCMV immune evasion and pathogenesis.
dc.relation.ispartofPLoS ONEen
dc.rightsCopyright: © 2022 Pantaleão et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectQH426 Geneticsen
dc.titleMolecular modelling of the HCMV IL-10 protein isoforms and analysis of their interaction with the human IL-10 receptoren
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews. St Andrews Bioinformatics Uniten
dc.description.statusPeer revieweden

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