The Plasmodium falciparum STEVOR Multigene Family Mediates Antigenic Variation of the Infected Erythrocyte

Makhtar Niang,Peter Rainer Preiser,Xue Yan Yam,Stephen John Rogerson

doi:10.1371/journal.ppat.1000307

Abstract

Modifications of the Plasmodium falciparum–infected red blood cell (iRBC) surface have been linked to parasite-associated pathology. Such modifications enable the parasite to establish long-lasting chronic infection by evading antibody mediate immune recognition and splenic clearance. With the exception of the well-demonstrated roles of var-encoded PfEMP1 in virulence and immune evasion, the biological significance of other variant surface antigens (rif and stevor) is largely unknown. While PfEMP1 and RIFIN have been located on the iRBC surface, recent studies have located STEVOR at the iRBC membrane where it may be exposed on the erythrocyte surface. To investigate the role of STEVOR in more detail, we have developed antibodies against two putative STEVOR proteins and used a combination of indirect immunofluorescence assays (IFA), live IFA, flow cytometry, as well as agglutination assays, which enable us to demonstrate that STEVOR is clonally variant at the surface of schizont stage parasites. Crucially, expression of different STEVOR on the surface of the iRBC changes the antigenic property of the parasite. Taken together, our data for the first time demonstrate that STEVOR plays a role in creating antigenic diversity of schizont stage parasites, thereby adding additional complexity to the immunogenic properties of the iRBC. Furthermore, it clearly demonstrates that to obtain a complete understanding of how parasite-induced pathology is linked to variation on the surface of the iRBC, focusing the interactions of multiple multigene families needs to be considered.

Highlights

During its maturation, the human malaria parasite Plasmodium falciparum extensively modifies the surface of the infected Red Blood Cell
The var, rifin and stevor multigene family coding for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), RIFIN and STEVOR respectively have been implicated in these processes and have been postulated to play a role in host-parasite interactions
PfEMP1 is expressed on the surface of infected Red Blood Cell (iRBC) [2,3] where it mediates the important pathogenic traits of both clonal antigenic variation and the adhesion of iRBCs to a variety of host receptors on the endothelium of the microvasculature leading to the obstruction of blood vessels and contributing to the pathology and disease severity seen with P. falciparum

Summary

Introduction

The human malaria parasite Plasmodium falciparum extensively modifies the surface of the infected Red Blood Cell (iRBC). These modifications have been linked to parasite associated pathology and are thought to enable the parasite to evade antibody mediated immune recognition and splenic clearance allowing the parasite to establish long lasting chronic infection [1]. PfEMP1 is expressed on the surface of iRBCs [2,3] where it mediates the important pathogenic traits of both clonal antigenic variation and the adhesion of iRBCs to a variety of host receptors on the endothelium of the microvasculature leading to the obstruction of blood vessels and contributing to the pathology and disease severity seen with P. falciparum. Based on the high similarity in size and structure between RIFIN and STEVOR proteins and their expression patterns in parasite blood stages, these proteins are speculated to be involved in antigenic variation [8,9]

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Conclusion