{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:50Z","timestamp":1753890950151,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p><jats:italic>Babesia orientalis<\/jats:italic>, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by <jats:italic>Rhipicephalus haemaphysaloides<\/jats:italic>. However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of <jats:italic>B. orientalis<\/jats:italic> merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in <jats:italic>B. orientalis<\/jats:italic>. We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system <jats:italic>in vitro<\/jats:italic> further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of <jats:italic>B. orientalis.<\/jats:italic> Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.<\/jats:p>","DOI":"10.3389\/fimmu.2021.623492","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T05:47:43Z","timestamp":1621230463000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Erythrocyte Adhesion of Merozoite Surface Antigen 2c1 Expressed During Extracellular Stages of Babesia orientalis"],"prefix":"10.3389","volume":"12","author":[{"given":"Zheng","family":"Nie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangsiqi","family":"Ao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Shu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muxiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyan","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"An","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yali","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangnan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junlong","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2018.11.002","article-title":"Unravelling the Cellular and Molecular Pathogenesis of Bovine Babesiosis: Is the Sky the Limit","volume":"49","author":"Suarez","year":"2019","journal-title":"Int J Parasitol"},{"key":"B2","article-title":"Babesiosis","volume-title":"Statpearls","author":"Zimmer","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2012.07.004","article-title":"Babesia: A World Emerging","volume":"12","author":"Schnittger","year":"2012","journal-title":"Genet Infect Evol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2010.06.012","article-title":"Recent Insights Into Alteration of Red Blood Cells by Babesia Bovis: Moovin\u2019 Forward","volume":"26","author":"Gohil","year":"2010","journal-title":"Trends Parasitol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(98)00076-9","article-title":"Apical Organelles and Host-Cell Invasion by Apicomplexa","volume":"28","author":"Dubremetz","year":"1998","journal-title":"Int J Parasitol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e35227","DOI":"10.1371\/journal.pone.0035227","article-title":"Gliding Motility of Babesia Bovis Merozoites Visualized by Time-Lapse Video Microscopy","volume":"7","author":"Asada","year":"2012","journal-title":"PloS One"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2013.12.011","article-title":"The Glycosylphosphatidylinositol-Anchored Protein Repertoire of Babesia Bovis and its Significance for Erythrocyte Invasion","volume":"5","author":"Rodriguez","year":"2014","journal-title":"Ticks Tick Borne Dis"},{"key":"B8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.vetpar.2006.01.038","article-title":"Genetic Basis for GPI-anchor Merozoite Surface Antigen Polymorphism of Babesia and Resulting Antigenic Diversity","volume":"138","author":"Carcy","year":"2006","journal-title":"Vet Parasitol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.12.6865-6870.2000","article-title":"Characterization of Allelic Variation in the Babesia Bovis Merozoite Surface Antigen 1 (MSA-1) Locus and Identification of a Cross-Reactive Inhibition-Sensitive MSA-1 Epitope","volume":"6812","author":"Suarez","year":"2000","journal-title":"Infect Immun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.260745","article-title":"Structural and Functional Characterization of Bc28.1, Major Erythrocyte-Binding Protein From Babesia Canis Merozoite Surface","volume":"287","author":"Yang","year":"2012","journal-title":"J Biol Chem"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182002002160","article-title":"Babesia Divergens: Cloning and Biochemical Characterization of Bd37","volume":"125","author":"Delbecq","year":"2002","journal-title":"Parasitology"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.02.006","article-title":"Invasion of Red Blood Cells by Malaria Parasites","volume":"124","author":"Cowman","year":"2006","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.08.019","article-title":"The Solution Structure of the Adhesion Protein Bd37 From Babesia Divergens Reveals Structural Homology With Eukaryotic Proteins Involved in Membrane Trafficking","volume":"375","author":"Delbecq","year":"2008","journal-title":"J Mol Biol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2009.09.024","article-title":"Babesia Bovis Contains an Abundant Parasite-Specific Protein-Free Glycerophosphatidylinositol and the Genes Predicted for its Assembly","volume":"167","author":"Rodr\u00edguez","year":"2010","journal-title":"Vet Parasitol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2009.09.023","article-title":"In Silico Predicted Conserved B-cell Epitopes in the Merozoite Surface Antigen-2 Family of B. Bovis are Neutralization Sensitive","volume":"167","author":"Dominguez","year":"2010","journal-title":"Vet Parasitol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"109275","DOI":"10.1016\/j.vetpar.2020.109275","article-title":"Schnittger L Et Al: Characterization of GASA-1, a New Vaccine Candidate Antigen of Babesia Bovis","volume":"287","author":"Flores","year":"2020","journal-title":"Vet Parasitol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetpar.2011.11.021","article-title":"Occurrence of Theileria and Babesia Species in Water Buffalo (Bubalus Babalis, Linnaeus, 1758) in the Hubei Province, South China","volume":"186","author":"He","year":"2012","journal-title":"Vet Parasitol"},{"key":"B18","first-page":"61","article-title":"An Investigation of Water Buffalo Babesiosis in Hubei Province V. Adult Rhipicephalus Haemaphysaloides Transmits the Parasites Transovarially","volume":"1","author":"Liu","year":"1989","journal-title":"Chin J Vet Sci"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-020-06877-z","article-title":"An X Et Al: Characterization of the Variable Merozoite Surface Antigen (VMSA) Gene Family of Babesia Orientalis","volume":"119","author":"Nie","year":"2020","journal-title":"Parasitol Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.11.7180-7189.2005","article-title":"Merozoite Surface Antigen 2 Proteins of Babesia Bovis Vaccine Breakthrough Isolates Contain a Unique Hypervariable Region Composed of Degenerate Repeats","volume":"73","author":"Berens","year":"2005","journal-title":"Infect Immun"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00032-06","article-title":"The Babesia Bovis Merozoite Surface Antigen 1 Hypervariable Region Induces Surface-Reactive Antibodies That Block Merozoite Invasion","volume":"74","author":"LeRoith","year":"2006","journal-title":"Infect Immun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1042\/bj20030622","article-title":"Definition of Structural Elements in Plasmodium Vivax and P. Knowlesi Duffy-binding Domains Necessary for Erythrocyte Invasion","volume":"374","author":"Singh","year":"2003","journal-title":"Biochem J"},{"key":"B23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1186\/s13071-018-3038-7","article-title":"The MEP Pathway in Babesia Orientalis Apicoplast, a Potential Target for Anti-Babesiosis Drug Development","volume":"11","author":"He","year":"2018","journal-title":"Parasit Vectors"},{"key":"B24","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s13071-019-3457-0","article-title":"Luo X Et Al: Identification of a Novel Thrombospondin-Related Anonymous Protein (BoTRAP2) From Babesia Orientalis","volume":"12","author":"Zhan","year":"2019","journal-title":"Parasite Vector"},{"key":"B25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/S0166-6851(00)00206-1","article-title":"Identification of a Novel Antigenic Domain of Plasmodium Falciparum Merozoite Surface Protein-1 That Specifically Binds to Human Erythrocytes and Inhibits Parasite Invasion, In Vitro","volume":"108","author":"Nikodem","year":"2000","journal-title":"Mol Biochem Parasitol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3370","DOI":"10.1038\/srep03370","article-title":"High-Density Distributed Electrode Network, a Multi-Functional Electroporation Method for Delivery of Molecules of Different Sizes","volume":"3","author":"Wu","year":"2013","journal-title":"Sci Rep"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2016.04.021","article-title":"Genetic Diversity and Antigenicity Variation of Babesia Bovis Merozoite Surface Antigen-1 (MSA-1) in Thailand","volume":"41","author":"Tattiyapong","year":"2016","journal-title":"Infection Genet evolution: Infect Genet Evol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"102152","DOI":"10.1016\/j.parint.2020.102152","article-title":"A Novel 53\u00a0kDa Protein (BoP53) in Babesia Orientalis Poses the Immunoreactivity Using the Infection Serum","volume":"78","author":"Shu","year":"2020","journal-title":"Parasitol Int"},{"key":"B29","doi-asserted-by":"publisher","first-page":"102106","DOI":"10.1016\/j.parint.2020.102106","article-title":"Nie Z Et Al: Identification and Characterizations of a Rhoptries Neck Protein 5 (BoRON5) in Babesia Orientalis","volume":"77","author":"Tian","year":"2020","journal-title":"Parasitol Int"},{"key":"B30","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1186\/s13071-018-3018-y","article-title":"Wang S Et Al: Characterization of a Novel Secretory Spherical Body Protein in Babesia Orientalis and Babesia Orientalis-Infected Erythrocytes","volume":"11","author":"Guo","year":"2018","journal-title":"Parasite Vector"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1002725","DOI":"10.1371\/journal.ppat.1002725","article-title":"Shedding of TRAP by a Rhomboid Protease From the Malaria Sporozoite Surface is Essential for Gliding Motility and Sporozoite Infectivity","volume":"8","author":"Ejigiri","year":"2012","journal-title":"PloS Pathog"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.698282","article-title":"Multiple Plasmodium Falciparum Merozoite Surface Protein 1 Complexes Mediate Merozoite Binding to Human Erythrocytes","volume":"291","author":"Lin","year":"2016","journal-title":"J Biol Chem"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e3085","DOI":"10.1371\/journal.pone.0003085","article-title":"Formation of the Food Vacuole in Plasmodium Falciparum: A Potential Role for the 19 kDa Fragment of Merozoite Surface Protein 1 (MSP1(19))","volume":"3","author":"Dluzewski","year":"2008","journal-title":"PloS One"},{"key":"B34","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1186\/1475-2875-9-77","article-title":"Antibodies Against Multiple Merozoite Surface Antigens of the Human Malaria Parasite Plasmodium Falciparum Inhibit Parasite Maturation and Red Blood Cell Invasion","volume":"9","author":"Woehlbier","year":"2010","journal-title":"Malar J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00866-13","article-title":"Sequential Processing of Merozoite Surface Proteins During and After Erythrocyte Invasion by Plasmodium Falciparum","volume":"82","author":"Boyle","year":"2014","journal-title":"Infect Immun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuw001","article-title":"Merozoite Surface Proteins in Red Blood Cell Invasion, Immunity and Vaccines Against Malaria","volume":"40","author":"Beeson","year":"2016","journal-title":"FEMS Microbiol Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01795-14","article-title":"Functional Analysis of Rhomboid Proteases During Toxoplasma Invasion","volume":"5","author":"Shen","year":"2014","journal-title":"mBio"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M604344200","article-title":"A Conserved Subtilisin Protease Identified in Babesia Divergens Merozoites","volume":"281","author":"Montero","year":"2006","journal-title":"J Biol Chem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.10.010","article-title":"The Repertoire of Serine Rhomboid Proteases of Piroplasmids of Importance to Animal and Human Health","volume":"68","author":"Gallenti","year":"2021","journal-title":"Int J Parasitol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.623492\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T05:47:48Z","timestamp":1621230468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.623492\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2021.623492"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.623492","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"article-number":"623492"}}