{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:04:48Z","timestamp":1789139088694,"version":"build-2803163510"},"reference-count":55,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T00:00:00Z","timestamp":1590019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008050","name":"Fundaci\u00f3n Cellex","doi-asserted-by":"publisher","award":["FC2007"],"award-info":[{"award-number":["FC2007"]}],"id":[{"id":"10.13039\/100008050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,6,9]]},"abstract":"<jats:p>\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    , the most widely distributed human malaria parasite, causes severe clinical syndromes despite low peripheral blood parasitemia. This conundrum is further complicated as cytoadherence in the microvasculature is still a matter of investigations. Previous reports in\n                    <jats:italic>Plasmodium knowlesi<\/jats:italic>\n                    , another parasite species shown to infect humans, demonstrated that variant genes involved in cytoadherence were dependent on the spleen for their expression. Hence, using a global transcriptional analysis of parasites obtained from spleen-intact and splenectomized monkeys, we identified 67\n                    <jats:italic>P. vivax<\/jats:italic>\n                    genes whose expression was spleen dependent. To determine their role in cytoadherence, two\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    transgenic lines expressing two variant proteins pertaining to VIR and Pv-FAM-D multigene families were used. Cytoadherence assays demonstrated specific binding to human spleen but not lung fibroblasts of the transgenic line expressing the VIR14 protein. To gain more insights, we expressed five\n                    <jats:italic>P. vivax<\/jats:italic>\n                    spleen-dependent genes as recombinant proteins, including members of three different multigene families (VIR, Pv-FAM-A, Pv-FAM-D), one membrane transporter (SECY), and one hypothetical protein (HYP1), and determined their immunogenicity and association with clinical protection in a prospective study of 383 children in Papua New Guinea. Results demonstrated that spleen-dependent antigens are immunogenic in natural infections and that antibodies to HYP1 are associated with clinical protection. These results suggest that the spleen plays a major role in expression of parasite proteins involved in cytoadherence and can reveal antigens associated with clinical protection, thus prompting a paradigm shift in\n                    <jats:italic>P. vivax<\/jats:italic>\n                    biology toward deeper studies of the spleen during infections.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1920596117","type":"journal-article","created":{"date-parts":[[2020,5,21]],"date-time":"2020-05-21T20:06:52Z","timestamp":1590091612000},"page":"13056-13065","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":43,"title":["<i>Plasmodium vivax<\/i>\n                    spleen-dependent genes encode antigens associated with cytoadhesion and clinical protection"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-0013","authenticated-orcid":false,"given":"Carmen","family":"Fernandez-Becerra","sequence":"first","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"},{"name":"Institut d\u2019Investigaci\u00f3 Germans Trias i Pujol, Badalona 08916, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Bernabeu","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-9696","authenticated-orcid":false,"given":"Ang\u00e9lica","family":"Castellanos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Cient\u00edfica Caucaseco, Cali, Valle, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna R.","family":"Correa","sequence":"additional","affiliation":[{"name":"Department of Computing and Mathematics FFCLRP, Ribeirao Preto, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 14040-900, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Obadia","sequence":"additional","affiliation":[{"name":"Department of Parasites and Insect Vectors, Institut Pasteur, Paris 75015, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Ramirez","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edmilson","family":"Rui","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Hentzschel","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"L\u00f3pez-Monta\u00f1\u00e9s","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ayllon-Hermida","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1511-8576","authenticated-orcid":false,"given":"Lorena","family":"Martin-Jaular","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleix","family":"Elizalde-Torrent","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Siba","sequence":"additional","affiliation":[{"name":"Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Z.","family":"V\u00eancio","sequence":"additional","affiliation":[{"name":"Department of Computing and Mathematics FFCLRP, Ribeirao Preto, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 14040-900, Brazil;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3434-9425","authenticated-orcid":false,"given":"Myriam","family":"Arevalo-Herrera","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n 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Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5278-3452","authenticated-orcid":false,"given":"Hernando A.","family":"del Portillo","sequence":"additional","affiliation":[{"name":"ISGlobal, Hospital Cl\u00ednic, Universitat de Barcelona, Barcelona 08036, Spain;"},{"name":"Institut d\u2019Investigaci\u00f3 Germans Trias i Pujol, Badalona 08916, Spain;"},{"name":"Instituci\u00f3 Catalana de Recerca I Estudis Avan\u00e7ats, Barcelona 08010, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,5,21]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4269\/ajtmh.16-0141","article-title":"Global epidemiology of Plasmodium vivax","volume":"95","author":"Howes R. 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