title: STEVOR is a Plasmodium falciparum erythrocyte binding protein that mediates merozoite invasion and rosetting.
abstract: Variant surface antigens play an important role in Plasmodium falciparum malaria pathogenesis and in immune evasion by the parasite. Although most work to date has focused on P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1), two other multigene families encoding STEVOR and RIFIN are expressed in invasive merozoites and on the infected erythrocyte surface. However, their role during parasite infection remains to be clarified. Here we report that STEVOR functions as an erythrocyte-binding protein that recognizes Glycophorin C (GPC) on the red blood cell (RBC) surface and that its binding correlates with the level of GPC on the RBC surface. STEVOR expression on the RBC leads to PfEMP1-independent binding of infected RBCs to uninfected RBCs (rosette formation), while antibodies targeting STEVOR in the merozoite can effectively inhibit invasion. Our results suggest a PfEMP1-independent role for STEVOR in enabling infected erythrocytes at the schizont stage to form rosettes and in promoting merozoite invasion.
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Makhtar
authors.initials: M
authors.lastname: Niang
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Amy Kristine
authors.initials: AK
authors.lastname: Bei
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Kripa Gopal
authors.initials: KG
authors.lastname: Madnani
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Shaaretha
authors.initials: S
authors.lastname: Pelly
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Selasi
authors.initials: S
authors.lastname: Dankwa
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Usheer
authors.initials: U
authors.lastname: Kanjee
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Karthigayan
authors.initials: K
authors.lastname: Gunalan
authors.affiliation: Singapore-MIT Alliance for Research and Technology (SMART)-Interdisciplinary Research Group in Infectious Diseases, Singapore 117456, Singapore.
authors.forename: Anburaj
authors.initials: A
authors.lastname: Amaladoss
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Kim Pin
authors.initials: KP
authors.lastname: Yeo
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Ndeye Sakha
authors.initials: NS
authors.lastname: Bob
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore 117545, Singapore; Singapore Immunology Network, A(∗)STAR, Singapore 138648, Singapore.
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Manoj Theodore
authors.initials: MT
authors.lastname: Duraisingh
authors.affiliation: Nanyang Technological University, School of Biological Sciences, 60 Nanyang Drive, Singapore 637551, Singapore. Electronic address: prpreiser@ntu.edu.sg.
authors.forename: Peter Rainer
authors.initials: PR
authors.lastname: Preiser
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004912:Erythrocytes / Q000469:parasitology*; D006021:Glycophorins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D052940:Merozoites / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; C066001:Duffy antigen binding protein, Plasmodium; D006021:Glycophorins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C474556:STEVOR antigen, Plasmodium falciparum; D037521:Virulence Factors