{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:29:05Z","timestamp":1793780945906,"version":"4.6.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"MEXT Grants-in-Aid for Scientific Research, Japan","award":["18K07088"],"award-info":[{"award-number":["18K07088"]}]},{"name":"Nagasaki University WISE Programme, Japan"},{"name":"MEXT Subsidies for Promoting National University Reform 2021, Japan"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Zoonotic malaria due to <jats:italic>Plasmodium knowlesi<\/jats:italic> infection in Southeast Asia is sometimes life-threatening. Post-mortem examination of human <jats:italic>knowlesi<\/jats:italic> malaria cases showed sequestration of <jats:italic>P. knowlesi<\/jats:italic>-infected red blood cells (iRBCs) in blood vessels, which has been proposed to be linked to disease severity. This sequestration is likely mediated by the cytoadhesion of parasite-iRBCs to vascular endothelial cells; however, the responsible parasite ligands remain undetermined. This study selected <jats:italic>P. knowlesi<\/jats:italic> lines with increased iRBC cytoadhesion activity by repeated panning against human umbilical vein endothelial cells (HUVECs). Transcriptome analysis revealed that the transcript level of one gene, encoding a Schizont Infected Cell Agglutination (SICA) protein, herein termed SICA-HUVEC, was more than 100-fold increased after the panning. Transcripts of other <jats:italic>P. knowlesi<\/jats:italic> proteins were also significantly increased, such as PIR proteins exported to the iRBC cytosol, suggesting their potential role in increasing cytoadhesion activity. Transgenic <jats:italic>P. knowlesi<\/jats:italic> parasites expressing Myc-fused SICA-HUVEC increased cytoadhesion activity following infection of monkey as well as human RBCs, confirming that SICA-HUVEC conveys activity to bind to HUVECs.<\/jats:p>","DOI":"10.1038\/s41598-022-19199-0","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T09:02:58Z","timestamp":1662109378000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SICA-mediated cytoadhesion of Plasmodium knowlesi-infected red blood cells to human umbilical vein endothelial cells"],"prefix":"10.1038","volume":"12","author":[{"given":"Huai","family":"Chuang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miako","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amuza Byaruhanga","family":"Lucky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Katakai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kawai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Kaneko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"19199_CR1","unstructured":"World Health Organization. World Malaria Report 2021 (World Health Organization, 2021). ISBN: 978-92-4-004049-6."},{"issue":"9414","key":"19199_CR2","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1016\/s0140-6736(04)15836-4","volume":"363","author":"B Singh","year":"2004","unstructured":"Singh, B. et al. A large focus of naturally acquired Plasmodium knowlesi infections in human beings. Lancet 363(9414), 1017\u20131024. https:\/\/doi.org\/10.1016\/s0140-6736(04)15836-4 (2004).","journal-title":"Lancet"},{"issue":"5","key":"19199_CR3","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.jmii.2019.05.012","volume":"52","author":"MT Zaw","year":"2019","unstructured":"Zaw, M. T. & Lin, Z. Human Plasmodium knowlesi infections in South-East Asian countries. J. Microbiol. Immunol. Infect. 52(5), 679\u2013684. https:\/\/doi.org\/10.1016\/j.jmii.2019.05.012 (2019).","journal-title":"J. Microbiol. Immunol. Infect."},{"issue":"4","key":"19199_CR4","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1007\/s10393-019-01395-6","volume":"16","author":"G Davidson","year":"2019","unstructured":"Davidson, G., Chua, T. H., Cook, A., Speldewinde, P. & Weinstein, P. The role of ecological linkage mechanisms in Plasmodium knowlesi transmission and spread. EcoHealth 16(4), 594\u2013610. https:\/\/doi.org\/10.1007\/s10393-019-01395-6 (2019).","journal-title":"EcoHealth"},{"issue":"2","key":"19199_CR5","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1128\/cmr.00079-12","volume":"26","author":"B Singh","year":"2013","unstructured":"Singh, B. & Daneshvar, C. Human infections and detection of Plasmodium knowlesi. Clin. Microbiol. Rev. 26(2), 165\u2013184. https:\/\/doi.org\/10.1128\/cmr.00079-12 (2013).","journal-title":"Clin. Microbiol. Rev."},{"issue":"10","key":"19199_CR6","doi-asserted-by":"publisher","first-page":"1703","DOI":"10.1093\/cid\/ciz011","volume":"69","author":"GS Rajahram","year":"2019","unstructured":"Rajahram, G. S. et al. Deaths from Plasmodium knowlesi malaria: Case series and systematic review. Clin. Infect. Dis. 69(10), 1703\u20131711. https:\/\/doi.org\/10.1093\/cid\/ciz011 (2019).","journal-title":"Clin. Infect. Dis."},{"issue":"4","key":"19199_CR7","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1203\/PDR.0b013e3181eee738","volume":"68","author":"R Idro","year":"2010","unstructured":"Idro, R., Marsh, K., John, C. C. & Newton, C. R. Cerebral malaria: Mechanisms of brain injury and strategies for improved neurocognitive outcome. Pediatr. Res. 68(4), 267\u2013274. https:\/\/doi.org\/10.1203\/PDR.0b013e3181eee738 (2010).","journal-title":"Pediatr. Res."},{"issue":"7","key":"19199_CR8","doi-asserted-by":"publisher","first-page":"1463","DOI":"10.1016\/j.biocel.2008.12.012","volume":"41","author":"ND Pasternak","year":"2009","unstructured":"Pasternak, N. D. & Dzikowski, R. PfEMP1: An antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum. Int. J. Biochem. Cell. Biol. 41(7), 1463\u20131466. https:\/\/doi.org\/10.1016\/j.biocel.2008.12.012 (2009).","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"19199_CR9","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1475-2875-9-10","volume":"9","author":"J Cox-Singh","year":"2010","unstructured":"Cox-Singh, J. et al. Severe malaria\u2014A case of fatal Plasmodium knowlesi infection with post-mortem findings: A case report. Malar. J. 9, 10. https:\/\/doi.org\/10.1186\/1475-2875-9-10 (2010).","journal-title":"Malar. J."},{"issue":"2","key":"19199_CR10","doi-asserted-by":"publisher","first-page":"188","DOI":"10.4269\/ajtmh.2003.69.188","volume":"69","author":"H Ozwara","year":"2003","unstructured":"Ozwara, H. et al. Experimental infection of the olive baboon (Papio anubis) with Plasmodium knowlesi: Severe disease accompanied by cerebral involvement. Am. J. Trop. Med. Hyg. 69(2), 188\u2013194. https:\/\/doi.org\/10.4269\/ajtmh.2003.69.188 (2003).","journal-title":"Am. J. Trop. Med. Hyg."},{"issue":"3","key":"19199_CR11","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1093\/cid\/ciy065","volume":"67","author":"MJ Grigg","year":"2018","unstructured":"Grigg, M. J. et al. Age-related clinical spectrum of Plasmodium knowlesi malaria and predictors of severity. Clin. Infect. Dis. 67(3), 350\u2013359. https:\/\/doi.org\/10.1093\/cid\/ciy065 (2018).","journal-title":"Clin. Infect. Dis."},{"issue":"2","key":"19199_CR12","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/s1097-2765(00)80304-4","volume":"3","author":"B al-Khedery","year":"1999","unstructured":"al-Khedery, B., Barnwell, J. W. & Galinski, M. R. Antigenic variation in malaria: A 3\u2032 genomic alteration associated with the expression of a P. knowlesi variant antigen. Mol. Cell 3(2), 131\u2013141. https:\/\/doi.org\/10.1016\/s1097-2765(00)80304-4 (1999).","journal-title":"Mol. Cell"},{"issue":"1","key":"19199_CR13","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1017\/s0031182017001329","volume":"145","author":"SA Lapp","year":"2018","unstructured":"Lapp, S. A. et al. PacBio assembly of a Plasmodium knowlesi genome sequence with Hi-C correction and manual annotation of the SICAvar gene family. Parasitology 145(1), 71\u201384. https:\/\/doi.org\/10.1017\/s0031182017001329 (2018).","journal-title":"Parasitology"},{"issue":"11","key":"19199_CR14","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1084\/jem.20041392","volume":"201","author":"G Winter","year":"2005","unstructured":"Winter, G. et al. SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes. J. Exp. Med. 201(11), 1853\u20131863. https:\/\/doi.org\/10.1084\/jem.20041392 (2005).","journal-title":"J. Exp. Med."},{"issue":"3","key":"19199_CR15","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1111\/j.1462-5822.2011.01726.x","volume":"14","author":"M Bernabeu","year":"2012","unstructured":"Bernabeu, M. et al. Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor. Cell. Microbiol. 14(3), 386\u2013400. https:\/\/doi.org\/10.1111\/j.1462-5822.2011.01726.x (2012).","journal-title":"Cell. Microbiol."},{"issue":"10","key":"19199_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164272","volume":"11","author":"AB Lucky","year":"2016","unstructured":"Lucky, A. B. et al. Plasmodium knowlesi Skeleton-Binding Protein 1 localizes to the \u2018Sinton and Mulligan\u2019 stipplings in the cytoplasm of monkey and human erythrocytes. PLoS\u00a0One 11(10), e0164272. https:\/\/doi.org\/10.1371\/journal.pone.0164272 (2016).","journal-title":"PLoS\u00a0One"},{"issue":"4","key":"19199_CR17","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/j.parint.2018.04.005","volume":"67","author":"KK Asare","year":"2018","unstructured":"Asare, K. K. et al. The Plasmodium knowlesi MAHRP2 ortholog localizes to structures connecting Sinton Mulligan\u2019s clefts in the infected erythrocyte. Parasitol. Int. 67(4), 481\u2013492. https:\/\/doi.org\/10.1016\/j.parint.2018.04.005 (2018).","journal-title":"Parasitol. Int."},{"issue":"4","key":"19199_CR18","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.mib.2006.06.006","volume":"9","author":"SM Kraemer","year":"2006","unstructured":"Kraemer, S. M. & Smith, J. D. A family affair: var genes, PfEMP1 binding, and malaria disease. Curr. Opin. Microbiol. 9(4), 374\u2013380. https:\/\/doi.org\/10.1016\/j.mib.2006.06.006 (2006).","journal-title":"Curr. Opin. Microbiol."},{"issue":"4","key":"19199_CR19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034509","volume":"7","author":"K Chotivanich","year":"2012","unstructured":"Chotivanich, K. et al. Plasmodium vivax adherence to placental glycosaminoglycans. PLoS\u00a0One 7(4), e34509. https:\/\/doi.org\/10.1371\/journal.pone.0034509 (2012).","journal-title":"PLoS\u00a0One"},{"key":"19199_CR20","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1475-2875-11-33","volume":"11","author":"FA Fatih","year":"2012","unstructured":"Fatih, F. A. et al. Cytoadherence and virulence\u2014The case of Plasmodium knowlesi malaria. Malar. J. 11, 33. https:\/\/doi.org\/10.1186\/1475-2875-11-33 (2012).","journal-title":"Malar. J."},{"issue":"2","key":"19199_CR21","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1073\/pnas.1216457110","volume":"110","author":"RW Moon","year":"2013","unstructured":"Moon, R. W. et al. Adaptation of the genetically tractable malaria pathogen Plasmodium knowlesi to continuous culture in human erythrocytes. Proc. Natl. Acad. Sci. U.S.A. 110(2), 531\u2013536. https:\/\/doi.org\/10.1073\/pnas.1216457110 (2013).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"19199_CR22","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2021.804417","volume":"12","author":"W-C Lee","year":"2022","unstructured":"Lee, W.-C. et al. Cytoadherence properties of Plasmodium knowlesi-infected erythrocytes. Front. Microbiol. 12, 804417. https:\/\/doi.org\/10.3389\/fmicb.2021.804417 (2022).","journal-title":"Front. Microbiol."},{"issue":"15","key":"19199_CR23","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201800315","volume":"19","author":"AK Madugundu","year":"2019","unstructured":"Madugundu, A. K. et al. Integrated transcriptomic and proteomic analysis of primary human umbilical vein endothelial cells. Proteomics 19(15), e1800315. https:\/\/doi.org\/10.1002\/pmic.201800315 (2019).","journal-title":"Proteomics"},{"issue":"2","key":"19199_CR24","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s10616-013-9560-8","volume":"66","author":"H Liao","year":"2014","unstructured":"Liao, H. et al. Effects of long-term serial cell passaging on cell spreading, migration, and cell-surface ultrastructures of cultured vascular endothelial cells. Cytotechnology 66(2), 229\u2013238. https:\/\/doi.org\/10.1007\/s10616-013-9560-8 (2014).","journal-title":"Cytotechnology"},{"issue":"3","key":"19199_CR25","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.jbiotec.2003.10.001","volume":"107","author":"Y Sasaki","year":"2004","unstructured":"Sasaki, Y. et al. Evidence for high specificity and efficiency of multiple recombination signals in mixed DNA cloning by the Multisite Gateway system. J. Biotechnol. 107(3), 233\u2013243. https:\/\/doi.org\/10.1016\/j.jbiotec.2003.10.001 (2004).","journal-title":"J. Biotechnol."},{"issue":"2","key":"19199_CR26","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1111\/j.1365-2958.2005.04699.x","volume":"57","author":"GG van Dooren","year":"2005","unstructured":"van Dooren, G. G. et al. Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol. Microbiol. 57(2), 405\u2013419. https:\/\/doi.org\/10.1111\/j.1365-2958.2005.04699.x (2005).","journal-title":"Mol. Microbiol."},{"issue":"2","key":"19199_CR27","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.parint.2012.12.002","volume":"62","author":"T Sakura","year":"2013","unstructured":"Sakura, T., Yahata, K. & Kaneko, O. The upstream sequence segment of the C-terminal cysteine-rich domain is required for microneme trafficking of Plasmodium falciparum erythrocyte binding antigen 175. Parasitol. Int. 62(2), 157\u2013164. https:\/\/doi.org\/10.1016\/j.parint.2012.12.002 (2013).","journal-title":"Parasitol. Int."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19199-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19199-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19199-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T10:14:18Z","timestamp":1662113658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-022-19199-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,2]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["19199"],"URL":"https:\/\/doi.org\/10.1038\/s41598-022-19199-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,2]]},"assertion":[{"value":"24 January 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14942"}}