Open AccessDiscovery of a novel and conserved P lasmodium falciparum exported protein that is important for adhesion of PfEMP 1 at the surface of infected erythrocytes
Author(s) -
Nacer Adéla,
Claes Aurélie,
Roberts Amy,
ScheidigBenatar Christine,
Sakamoto Hiroshi,
Ghorbal Mehdi,
LopezRubio JoseJuan,
Mattei Denise
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12430
Subject(s) - biology , plasmodium falciparum , virulence , gene , complementation , subtelomere , adhesion , cell adhesion , mutant , microbiology and biotechnology , genetics , chromosome , cell , immunology , malaria , chemistry , organic chemistry
Summary P lasmodium falciparum virulence is linked to its ability to sequester in post‐capillary venules in the human host. P lasmodium falciparum erythrocyte membrane protein 1 ( PfEMP 1) 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 D 10 and T 9‐96. Similar to the cytoadherent reference line FCR 3, D 10 strain expresses PfEMP 1 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 D 10 complementation studies that are predicted to code for proteins exported to the red blood cell. We identified a novel single copy gene ( PF 3 D 7_0936500) restricted to P . falciparum that restores adhesion to CD 36, termed here virulence‐associated protein 1 ( Pfvap1 ). Protein knockdown and gene knockout experiments confirmed a role of PfVAP 1 in the adhesion process in FCR 3 parasites. PfVAP 1 is co‐exported with PfEMP 1 into the host cell via vesicle‐like structures called M aurer's clefts. This study identifies a novel highly conserved parasite molecule that contributes to parasite virulence possibly by assisting PfEMP 1 to establish functional adhesion at the host cell surface.