Switches in expression of plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes

Abstract

Plasmodium falciparum expresses on the host erythrocyte surface clonally variant antigens and ligands that mediate adherence to endothelial receptors. Both are central to pathogenesis, since they allow chronicity of infection and lead to concentration of infected erythrocytes in cerebral vessels. Here we show that expression of variant antigenic determinants is correlated with expression of individual members of a large, multigene family named var. Each var gene contains copies of a motif that has been previously shown to bind diverse host receptors; expression of a specific var gene correlated with binding to ICAM-1. Thus, our findings are consistent with the involvement of var genes in antigenic variation and binding to endothelium.

Allelic forms of the knob associated histidine‐rich protein gene of Plasmodium falciparum

“…Recently three labs have independently cloned the gene for a highly variable knob antigen called as P falciparum erythrocyte membrane protein-I (PFEMP-1) [10][11][12]. It has been speculated that the C-terminal acidic domain of PFEMP-1 must be interacting with the positively charged KAHRP through salt bridges [11].…”

Virulence in malaria: an evolutionary viewpoint

“…These antigens are highly variable both between parasite clones and within clones owing to an antigenic switching mechanism. This variability is afforded by the multiple copies in the genome of their coding gene, denoted var (Baruch et al 1995;Smith et al 1995;Su et al 1995). These antigens are recognized by the immune system in a highly variantspecific way (Marsh & Howard 1986;Forsyth et al 1989;Newbold et al 1992;Iqbal et al 1993;Reeder et al 1994;Giha et al 1998;Bull et al 1999;Giha et al 1999;Nielsen et al 2002;Ofori et al 2002) although there appears to be some cross-reactivity between variants (Aguiar et al 1992;Chattopadhyay et al 2003).…”

A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

“…The subsequent accumulation of infected RBCs in the microvasculature is largely responsible for malaria-associated morbidity and mortality. This sequestration of IRBCs is mediated by the parasite protein P. falciparum erythrocyte membrane protein 1 (PfEMP-1), which is exported to the surface of the IRBCs and is encoded by a family of variant antigens (Baruch et al, 1995;Smith et al, 1995;Su et al, 1995). Because human RBCs are devoid of a functional protein trafficking system, the parasite has to establish a protein export system in the host cell before PfEMP-1 can be displayed on the surface of the infected cell.…”