Abstract
BackgroundThe expression of the clonally variant virulence factor PfEMP1 mediates the sequestration of Plasmodium falciparum infected erythrocytes in the host vasculature and contributes to chronic infection. Non-cytoadherent parasites with a chromosome 9 deletion lack clag9, a gene linked to cytoadhesion in previous studies. Here we present new clag9 data that challenge this view and show that surface the non-cytoadherence phenotype is linked to the expression of a non-functional PfEMP1.Methodology/Principal FindingsLoss of adhesion in P. falciparum D10, a parasite line with a large chromosome 9 deletion, was investigated. Surface iodination analysis of non-cytoadherent D10 parasites and COS-7 surface expression of the CD36-binding PfEMP1 CIDR1α domain were performed and showed that these parasites express an unusual trypsin-resistant, non-functional PfEMP1 at the erythrocyte surface. However, the CIDR1α domain of this var gene expressed in COS-7 cells showed strong binding to CD36. Atomic Force Microscopy showed a slightly modified D10 knob morphology compared to adherent parasites. Trafficking of PfEMP1 and KAHRP remained functional in D10. We link the non-cytoadherence phenotype to a chromosome 9 breakage and healing event resulting in the loss of 25 subtelomeric genes including clag9. In contrast to previous studies, knockout of the clag9 gene from 3D7 did not interfere with parasite adhesion to CD36.Conclusions/SignificanceOur data show the surface expression of non-functional PfEMP1 in D10 strongly indicating that genes other than clag9 deleted from chromosome 9 are involved in this virulence process possibly via post-translational modifications.
Highlights
An important factor contributing to the virulence of Plasmodium falciparum is the ability of parasitized red blood cells (PRBC) to adhere to receptors such as CD36 or ICAM-1 expressed on the surface of endothelial cells, or chondroitin sulphate A (CSA) expressed on placental syncytiotrophoblasts
In D10 PfEMP1 is trafficked to the surface of PRBC but is unable to bind to host adhesion receptors
Even repeated panning experiments on C32 cells or recombinant CD36 bound to plastic dishes did not yield any increase in binding, showing that no other var gene is able to restore the adhesion phenotype
Summary
An important factor contributing to the virulence of Plasmodium falciparum is the ability of parasitized red blood cells (PRBC) to adhere to receptors such as CD36 or ICAM-1 expressed on the surface of endothelial cells, or chondroitin sulphate A (CSA) expressed on placental syncytiotrophoblasts (see [1] for a review). The variant antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the predominant ligand responsible for adhesion to host endothelial receptors and is essential for parasite survival and establishing chronic infection [2]. The expression of the clonally variant virulence factor PfEMP1 mediates the sequestration of Plasmodium falciparum infected erythrocytes in the host vasculature and contributes to chronic infection. We present new clag data that challenge this view and show that surface the non-cytoadherence phenotype is linked to the expression of a nonfunctional PfEMP1
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
