{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:54:15Z","timestamp":1782370455560,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012434","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000}}],"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["084226"],"award-info":[{"award-number":["084226"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204052\/Z\/16\/Z"],"award-info":[{"award-number":["204052\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["218492\/Z\/19\/Z"],"award-info":[{"award-number":["218492\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["203077\/Z\/16\/Z"],"award-info":[{"award-number":["203077\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Plasmodium falciparum<\/jats:italic> erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by <jats:italic>var<\/jats:italic> genes, that mediates binding of infected erythrocytes to human cells and plays a key role in parasite immune evasion and malaria pathology. The increased availability of parasite genome sequence data has revolutionised the study of PfEMP1 diversity across multiple <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> isolates. However, making functional sense of genomic data relies on the ability to infer binding phenotype from <jats:italic>var<\/jats:italic> gene sequence. For <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> rosetting, the binding of infected erythrocytes to uninfected erythrocytes, the analysis of <jats:italic>var<\/jats:italic> gene\/PfEMP1 sequences encoding the phenotype is limited, with only eight rosette-mediating PfEMP1 variants described to date. These known rosetting PfEMP1 variants fall into two types, characterised by N-terminal domains known as \u201cdomain cassette\u201d 11 (DC11) and DC16. Here we test the hypothesis that DC11 and DC16 are the only PfEMP1 types in the <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic> genome that mediate rosetting, by examining a set of thirteen recent culture-adapted Kenyan parasite lines. We first analysed the <jats:italic>var<\/jats:italic> gene\/PfEMP1 repertoires of the Kenyan lines and identified an average of three DC11 or DC16 PfEMP1 variants per genotype. <jats:italic>In vitro<\/jats:italic> rosette selection of the parasite lines yielded four with a high rosette frequency, and analysis of their <jats:italic>var<\/jats:italic> gene transcription, infected erythrocyte PfEMP1 surface expression, rosette disruption and erythrocyte binding function identified four novel rosette-mediating PfEMP1 variants. Two of these were of the predicted DC11 type (one showing the dual rosetting\/IgM-Fc-binding phenotype), whereas two contained DC15 (DBL\u03b11.2-CIDR\u03b11.5b) a PfEMP1 type not previously associated with rosetting. We also showed that a Thai parasite line expressing a DC8-like PfEMP1 binds to erythrocytes to form rosettes. Hence, these data expand current knowledge of rosetting mechanisms and emphasize that the PfEMP1 types mediating rosetting are more diverse than previously recognised.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012434","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T19:04:52Z","timestamp":1736795092000},"page":"e1012434","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype"],"prefix":"10.1371","volume":"21","author":[{"given":"Florence E.","family":"McLean","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian R.","family":"Omondi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouhoum","family":"Diallo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Otoboh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyne","family":"Kifude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdirahman I.","family":"Abdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq","family":"Ghumra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-1892","authenticated-orcid":true,"given":"J. Alexandra","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,13]]},"reference":[{"issue":"10","key":"ppat.1012434.ref001","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.pt.2022.08.001","article-title":"Evolving perspectives on rosetting in malaria","volume":"38","author":"WC Lee","year":"2022","journal-title":"Trends Parasitol"},{"issue":"6","key":"ppat.1012434.ref002","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1128\/iai.63.6.2323-2326.1995","article-title":"Plasmodium falciparum rosetting is associated with malaria severity in Kenya","volume":"63","author":"A Rowe","year":"1995","journal-title":"Infect Immun"},{"issue":"8729","key":"ppat.1012434.ref003","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/0140-6736(90)93174-N","article-title":"Human cerebral malaria: association with erythrocyte rosetting and lack of 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