{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:22:27Z","timestamp":1793316147769,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012583","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["15K18783"],"award-info":[{"award-number":["15K18783"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K15983"],"award-info":[{"award-number":["19K15983"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K19258"],"award-info":[{"award-number":["18K19258"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H03120"],"award-info":[{"award-number":["19H03120"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K08021"],"award-info":[{"award-number":["16K08021"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K06384"],"award-info":[{"award-number":["19K06384"]}],"id":[{"id":"10.13039\/501100001691","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>Babesia bovis<\/jats:italic> causes the most pathogenic form of babesiosis in cattle, resulting in high mortality in naive adults. This parasite invades red blood cells (RBCs) within the bovine hosts where they multiply and produce clinical disease. <jats:italic>Babesia bovis<\/jats:italic> exports numerous proteins into invaded RBCs changing its properties. Thus, the infected RBCs (iRBCs) are capable to cytoadhere in the microvasculature of internal organs and brain, leading to respiratory distress, neurologic signs, and mortality. Variant Erythrocyte Surface Antigen 1 (VESA1) is one of those exported proteins by <jats:italic>B. bovis<\/jats:italic> which represents a major virulence factor due to its central role in immune evasion by antigenic variation and intravascular parasite sequestration. VESA1 is a heterodimer protein encoded by <jats:italic>ves1\u03b1<\/jats:italic> and <jats:italic>ves1\u03b2<\/jats:italic> multigene family and localized on the ridges, the focal point for cytoadhesion. To gain further insights into the molecular mechanisms of cytoadhesion of <jats:italic>B. bovis<\/jats:italic>, we panned the parasites with bovine brain microvasculature endothelial cells, which resulted in obtaining several clones with different cytoadherence abilities. The transcriptome analysis of 2 high and 2 low cytoadherent clones revealed that <jats:italic>ves1\u03b1<\/jats:italic> sequences were diversified, likely resulting from genomic recombination. On the other hand, <jats:italic>ves1\u03b2<\/jats:italic> sequences were almost identical among these 4 clones. Insertion and expression of <jats:italic>ves1\u03b1<\/jats:italic> of a clone with high binding into <jats:italic>ef-1<\/jats:italic><jats:italic>\u03b1<\/jats:italic> locus of a low binding clone increased cytoadherence confirming the role of <jats:italic>ves1\u03b1<\/jats:italic> suggested by our transcriptome data. Whole genome sequencing of cytoadherent clones revealed active locus of <jats:italic>ves1<\/jats:italic> on chromosome 2. These results suggest that VESA1a proteins encoded by <jats:italic>ves1\u03b1<\/jats:italic> genes determine the cytoadherence strength of <jats:italic>B. bovis<\/jats:italic> and they are in the active site for recombination.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012583","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T17:48:42Z","timestamp":1745862522000},"page":"e1012583","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["ves1\u03b1 genes expression is the major determinant of Babesia bovis-infected erythrocytes cytoadhesion to endothelial cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-7393","authenticated-orcid":true,"given":"Hassan","family":"Hakimi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junya","family":"Yamagishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miako","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atefeh","family":"Fathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Seung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme G.","family":"Verocai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichiro","family":"Kawazu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0042-6856","authenticated-orcid":true,"given":"Masahito","family":"Asada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"issue":"4","key":"ppat.1012583.ref001","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1128\/CMR.16.4.622-636.2003","article-title":"Babesia divergens, a bovine blood parasite of veterinary and zoonotic importance","volume":"16","author":"A Zintl","year":"2003","journal-title":"Clin Microbiol Rev"},{"key":"ppat.1012583.ref002","article-title":"Babesiosis of cattle","author":"R 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