Analysis of PfEMP1—var Gene Sequences in Different Plasmodium falciparum Malarial Parasites

Aarti Ozarkar,D Prakash,Deepti Deobagkar,Dileep Deobagkar

doi:10.3814/2009/824949

Abstract

Plasmodium falciparum synthesizes P. falciparum erythrocyte membrane protein-1 (PfEMP-1), a product of the multicopy var gene family, which localizes on the surface of infected erythrocytes. This protein plays an important role in cytoadherence and immune evasion. Comparative analysis of the molecular sequences of the DBLα domain of the var gene from different isolates of the parasite reveals variations in the number of cysteines and presence of small conserved motifs like DGEA, RGD, GAG-binding motifs. Phylogenetic analysis while highlighting the extensive diversity leads to clustered them in separate clades far apart from each other. Discriminant factor analysis of physicochemical properties of amino acid sequences revealed that the aliphatic index, isoelectric point, and instability index have more effect in deciding the variance of different isolates sequences. The origin of diverse repertoire of the DBLα domain in the parasites highlights the complexity of host-parasite relationship in the context of parasite survival.

Highlights

Malaria has emerged as a major health problem especially in tropical and subtropical regions of the world [1]
Plasmodium falciparum synthesizes P. falciparum erythrocyte membrane protein-1 (PfEMP-1), a product of the multicopy var gene family, which localizes on the surface of infected erythrocytes
We have critically analyzed var gene sequences in terms of motifs, amino acid, physicochemical properties, and constructed phylogenetic trees from var gene sequences derived from parasite lines from India and Thailand and field isolates from Western part of India

Summary

Introduction

Malaria has emerged as a major health problem especially in tropical and subtropical regions of the world [1]. The gene has 60 copies; only one gene is expressed at a time This variant surface antigen has a major role in evasion of the host immune response and cytoadherence [3,4,5,6]. PfEMP1 acts as a ligand for host endothelial epithelial receptor This results in sequestration of infected erythrocytes in the microvasculature of the brain, placenta, and other organs thereby causing cerebral malaria and severe malaria. PfEMP1 is a virulence factor and plays an important role in pathophysiology of the disease (severe malaria and cerebral malaria) and enhances survival of the parasite. It has been considered as one of the vaccine targets [7]. DBLα domain is becoming the target of immunoepidemiological and vaccine production studies to analyze diversity in the parasite population’s worldwide [9]

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Results

Conclusion