{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:26:16Z","timestamp":1791203176974,"version":"4.2.0"},"reference-count":64,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,6,26]]},"abstract":"<jats:p>\n                    Cerebral malaria (CM) is a deadly complication of\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    infection, but specific interactions involved in cerebral homing of infected erythrocytes (IEs) are poorly understood. In this study,\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    -IEs were characterized for binding to primary human brain microvascular endothelial cells (HBMECs). Before selection, CD36 or ICAM-1\u2013binding parasites exhibited punctate binding to a subpopulation of HBMECs and binding was CD36 dependent. Panning of IEs on HBMECs led to a more dispersed binding phenotype and the selection of three\n                    <jats:italic>var<\/jats:italic>\n                    genes, including two that encode the tandem domain cassette 8 (DC8) and were non-CD36 binders. Multiple domains in the DC8 cassette bound to brain endothelium and the cysteine-rich interdomain region 1 inhibited binding of\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    -IEs by 50%, highlighting a key role for the DC8 cassette in cerebral binding. It is mysterious how deadly binding variants are maintained in the parasite population. Clonal parasite lines expressing the two brain-adherent DC8-\n                    <jats:italic>var<\/jats:italic>\n                    genes did not bind to any of the known microvascular receptors, indicating unique receptors are involved in cerebral binding. They could also adhere to brain, lung, dermis, and heart endothelial cells, suggesting cerebral binding variants may have alternative sequestration sites. Furthermore, young African children with CM or nonsevere control cases had antibodies to HBMEC-selected parasites, indicating they had been exposed to related variants during childhood infections. This analysis shows that specific\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    erythrocyte membrane protein 1 types are linked to cerebral binding and suggests a potential mechanism by which individuals may build up immunity to severe disease, in the absence of CM.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1120534109","type":"journal-article","created":{"date-parts":[[2012,5,23]],"date-time":"2012-05-23T00:50:18Z","timestamp":1337734218000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":189,"title":["A restricted subset of\n                    <i>var<\/i>\n                    genes mediates adherence of\n                    <i>Plasmodium falciparum<\/i>\n                    -infected erythrocytes to brain endothelial cells"],"prefix":"10.1073","volume":"109","author":[{"given":"Marion","family":"Avril","sequence":"first","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, WA 98109-5219;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhai K.","family":"Tripathi","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Brazier","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, WA 98109-5219;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheryl","family":"Andisi","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\u2013Wellcome Trust Research Programme, 80108, Kilifi, Kenya;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel H.","family":"Janes","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, WA 98109-5219;"},{"name":"Department of Global Health, University of Washington, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya L.","family":"Soma","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, WA 98109-5219;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"David J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Bull","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute\u2013Wellcome Trust Research Programme, 80108, Kilifi, Kenya;"},{"name":"Nuffield Department of Clinical Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique F.","family":"Stins","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Seattle Biomedical Research Institute, Seattle, WA 98109-5219;"},{"name":"Department of Global Health, University of Washington, Seattle, WA 98109;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2012,5,22]]},"reference":[{"key":"e_1_1_2_17_8_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5267.1502"},{"key":"e_1_1_2_17_8_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03570.x"},{"key":"e_1_1_2_17_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/357689a0"},{"key":"e_1_1_2_17_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/415673a"},{"key":"e_1_1_2_17_8_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000933"},{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90054-3"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90056-X"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90055-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.4049\/jimmunol.149.6.2047","article-title":"Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum","volume":"149","author":"Biggs BA","year":"1992","unstructured":"BA Biggs, et al., Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. 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