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Virulence of malaria is associated with differential expression of Plasmodium falciparum var gene subgroups in a
Mirjam Kaestli1, Ian A Cockburn, Alfred Cortés
1Swiss Tropical Institute, Basel, Switzerland.
Abstract:
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a major pathogenicity factor in falciparum malaria that mediates cytoadherence. PfEMP1 is encoded by approximately 60 var genes per haploid genome. Most var genes are grouped into 3 subgroups: A, B, and C. Evidence is emerging that the specific expression of these subgroups has clinical significance. Using field samples from children from Papua New Guinea with severe, mild, and asymptomatic malaria, we compared proportions of transcripts of var groups, as determined by quantitative polymerase chain reaction. We found a significantly higher proportion of var group B transcripts in children with clinical malaria (mild and severe), whereas a large proportion of var group C transcripts was found in asymptomatic children. These data from naturally infected children clearly show that major differences exist in var gene expression between parasites causing clinical disease and those causing asymptomatic infections. Furthermore, parasites forming rosettes showed a significant up-regulation of var group A transcripts.
Insights
Var gene expression in Plasmodium falciparum differs between clinical and asymptomatic malaria. Group B var transcripts are higher in clinical cases, while Group C transcripts are prevalent in asymptomatic infections.
Area of Science:
- Malariology
- Molecular Biology
- Genetics
Background:
- Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key virulence factor in falciparum malaria, mediating cytoadherence.
- PfEMP1 is encoded by approximately 60 var genes, classified into three main subgroups: A, B, and C.
- Emerging evidence suggests that the differential expression of these var gene subgroups correlates with clinical outcomes.
Purpose of the Study:
- To investigate the association between var gene subgroup expression and the clinical presentation of falciparum malaria in children.
- To compare var gene expression profiles in parasites from children with severe, mild, and asymptomatic malaria.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) was used to determine the proportions of var group transcripts.
- Field samples were collected from children in Papua New Guinea with varying malaria severity.
Main Results:
- A significantly higher proportion of var group B transcripts was observed in children with clinical malaria (mild and severe).
- Asymptomatic infections were characterized by a higher proportion of var group C transcripts.
- Parasites forming rosettes showed a significant upregulation of var group A transcripts.
Conclusions:
- Distinct var gene expression patterns distinguish parasites causing clinical malaria from those causing asymptomatic infections.
- Var gene subgroup expression is a significant factor in the clinical manifestation of falciparum malaria.
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