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Band 3-mediated Plasmodium vivax invasion is associated with transcriptional variation in PvTRAg genes

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dc.contributor.author De Meulenaere, Katlijn
dc.contributor.author Prajapati, Surendra Kumar
dc.contributor.author Villasis Mayuri, Elizabeth Melisa
dc.contributor.author Cuypers, Bart
dc.contributor.author Kattenberg, Johanna Helena
dc.contributor.author Kasian, Bernadine
dc.contributor.author Laman, Moses
dc.contributor.author Robinson, Leanne J.
dc.contributor.author Gamboa Vilela, Dionicia Baziliza
dc.contributor.author Laukens, Kris
dc.contributor.author Rosanas-Urgell, Anna
dc.date.accessioned 2022-11-15T23:04:40Z
dc.date.available 2022-11-15T23:04:40Z
dc.date.issued 2022
dc.identifier.uri https://hdl.handle.net/20.500.12866/12580
dc.description.abstract The Plasmodium vivax reticulocyte invasion process is still poorly understood, with only a few receptor-ligand interactions identified to date. Individuals with the Southeast Asian ovalocytosis (SAO) phenotype have a deletion in the band 3 protein on the surface of erythrocytes, and are reported to have a lower incidence of clinical P. vivax malaria. Based on this observation, band 3 has been put forward as a receptor for P. vivax invasion, although direct proof is still lacking. In this study, we combined functional ex vivo invasion assays and transcriptome sequencing to uncover a band 3-mediated invasion pathway in P. vivax and potential band 3 ligands. Invasion by P. vivax field isolates was 67%-71% lower in SAO reticulocytes compared with non-SAO reticulocytes. Reticulocyte invasion was decreased by 40% and 27%-31% when blocking with an anti-band 3 polyclonal antibody and a PvTRAg38 peptide, respectively. To identify new band 3 receptor candidates, we mRNA-sequenced schizont-stage isolates used in the invasion assays, and observed high transcriptional variability in multigene and invasion-related families. Transcriptomes of isolates with low or high dependency on band 3 for invasion were compared by differential expression analysis, which produced a list of band 3 ligand candidates with high representation of PvTRAg genes. Our ex vivo invasion assays have demonstrated that band 3 is a P. vivax invasion receptor and confirm previous in vitro studies showing binding between PvTRAg38 and band 3, although the lower and variable inhibition levels observed suggest the involvement of other ligands. By coupling transcriptomes and invasion phenotypes from the same isolates, we identified a list of band 3 ligand candidates, of which the overrepresented PvTRAg genes are the most promising for future research. en_US
dc.language.iso eng
dc.publisher Frontiers Media
dc.relation.ispartofseries Frontiers in Cellular and Infection Microbiology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject P. vivax en_US
dc.subject Plasmodium vivax en_US
dc.subject Southeast Asian Ovalocytosis en_US
dc.subject SAO en_US
dc.subject transcriptome en_US
dc.subject differential expression analysis en_US
dc.subject malaria en_US
dc.subject band 3 en_US
dc.subject ex vivo invasion en_US
dc.subject RNA-seq en_US
dc.title Band 3-mediated Plasmodium vivax invasion is associated with transcriptional variation in PvTRAg genes en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3389/fcimb.2022.1011692
dc.relation.issn 2235-2988


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