title: Discovery of a novel and conserved Plasmodium falciparum exported protein that is important for adhesion of PfEMP1 at the surface of infected erythrocytes.
abstract: Plasmodium falciparum virulence is linked to its ability to sequester in post-capillary venules in the human host. Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is the main variant surface antigen implicated in this process. Complete loss of parasite adhesion is linked to a large subtelomeric deletion on chromosome 9 in a number of laboratory strains such as D10 and T9-96. Similar to the cytoadherent reference line FCR3, D10 strain expresses PfEMP1 on the surface of parasitized erythrocytes, however without any detectable cytoadhesion. To investigate which of the deleted subtelomeric genes may be implicated in parasite adhesion, we selected 12 genes for D10 complementation studies that are predicted to code for proteins exported to the red blood cell. We identified a novel single copy gene (PF3D7_0936500) restricted to P. falciparum that restores adhesion to CD36, termed here virulence-associated protein 1 (Pfvap1). Protein knockdown and gene knockout experiments confirmed a role of PfVAP1 in the adhesion process in FCR3 parasites. PfVAP1 is co-exported with PfEMP1 into the host cell via vesicle-like structures called Maurer's clefts. This study identifies a novel highly conserved parasite molecule that contributes to parasite virulence possibly by assisting PfEMP1 to establish functional adhesion at the host cell surface.
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Adéla
authors.initials: A
authors.lastname: Nacer
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Claes
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Amy
authors.initials: A
authors.lastname: Roberts
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Scheidig-Benatar
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakamoto
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghorbal
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Jose-Juan
authors.initials: JJ
authors.lastname: Lopez-Rubio
authors.affiliation: Biology of Parasite-Host Interactions Unit, Department of Parasites and Insect Vectors, Institut Pasteur, 25, Rue du Dr. Roux, Paris, F-75015, France.|INSERM U1201, 25, Rue du Dr. Roux, Paris, F-75015, France.|CNRS ERL9195, 25, Rue du Dr. Roux, Paris, F-75015, France.
authors.forename: Denise
authors.initials: D
authors.lastname: Mattei
mesh_terms: D002448:Cell Adhesion; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D005816:Genetic Complementation Test; D006801:Humans; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D017384:Sequence Deletion
chemical_list: D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum