Multiple var gene transcripts are expressed in Plasmodium falciparum infected erythrocytes selected for adhesion

The var genes of Plasmodium falciparum code for the antigenically variant erythrocyte membrane proteins 1 (PfEMP1), a major factor for cytoadherence and immune escape of the parasite. Herein, we analyzed the var gene transcript turnover in two ongoing, non-symptomatic infections at sequential time points during two weeks. The number of different circulating genomes was estimated by microsatellite analyses. In both infections, we observed a rapid turnover of plasmodial genotypes and var transcripts. The rapidly changing repertoire of var transcripts could have been caused either by swift elimination of circulating var-transcribing parasites stemming from different or identical genetic backgrounds, or by accelerated switching of var gene transcription itself.

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A distinct 5' flanking var gene region regulates Plasmodium falciparum variant erythrocyte surface antigen expression in placental malaria

Molecular Microbiology ◽

10.1046/j.1365-2958.2002.02999.x ◽

2002 ◽

Vol 45 (1) ◽

pp. 155-167 ◽

Cited By ~ 21

Author(s):

Aleida Vazquez-Macias ◽

Perla Martinez-Cruz ◽

Maria Cristina Castaneda-Patlan ◽

Christine Scheidig ◽

Jurg Gysin ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Surface Antigen ◽

Placental Malaria ◽

Antigen Expression ◽

Gene Region ◽

Erythrocyte Surface ◽

Surface Antigen Expression ◽

Var Gene

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The Plasmodium falciparum var gene switching rate, switching mechanism and patterns of parasite recrudescence described by mathematical modelling

Parasitology ◽

10.1017/s0031182001001160 ◽

2002 ◽

Vol 124 (3) ◽

pp. 225-235 ◽

Cited By ~ 43

Author(s):

S. PAGET-MCNICOL ◽

M. GATTON ◽

I. HASTINGS ◽

A. SAUL

Keyword(s):

Plasmodium Falciparum ◽

Chronic Infection ◽

Malaria Parasite ◽

Gene Repertoire ◽

Switching Rate ◽

Specific Immunity ◽

Parasite Survival ◽

Gene Switching ◽

Variant Antigen ◽

Var Gene

Recrudescing Plasmodium falciparum parasitaemia is attributed to the switching of PfEMP1, a variant antigen family encoded by the var gene repertoire, and the host's immune response. We have developed a mathematical model which incorporates var gene switching, and variant specific, non-variant specific and non-specific immunity. By conducting a sensitivity analysis of the model we have defined the parameter limits which produce chronic and recrudescing infections. We explore 3 switching mechanisms: ordered, random and uncoupled switching. We show that if var genes switch on and off independently at variable rates through the repertoire a chronic clinical infection is predicted. The fastest switching-on rate that produces a chronic infection is 0·03% per generation. The model predicts that non-variant specific immunity plays an important role in reducing disease severity. This work illustrates the complex relationship between the malaria parasite and its host and shows that var gene switching at rates substantially slower than 2% are essential for parasite survival.

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