Related Experiment Videos
Identification of a conserved Plasmodium falciparum var gene implicated in malaria in pregnancy
J Alexandra Rowe1, Sue A Kyes, Stephen J Rogerson
1Institute of Cell, Animal, and Population Biology, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, United Kingdom. Alex.Rowe@ed.ac.uk
Abstract:
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family is a highly polymorphic class of variant surface antigens encoded by var genes that play an important role in malaria pathogenesis. This report describes the unexpected finding that 1 of the var genes encoding a PfEMP1 variant that binds to the host receptor chondroitin sulfate A (CSA) and is implicated in malaria in pregnancy is well conserved among P. falciparum isolates worldwide. The N-terminal domains of this PfEMP1 variant are especially highly conserved, whereas the functional CSA binding domain is more variable. Analysis of var gene expression in placental parasites from primigravid women in Malawi did not support a role for this conserved gene in placental infection but identified a second commonly occurring var gene. These results indicate the need for reevaluation of previous assumptions of a minimal overlap between var gene repertoires from different parasite isolates.
Insights
A specific Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) gene, crucial for pregnancy malaria, is unexpectedly conserved globally. However, its role in placental infection requires further investigation, challenging prior assumptions about parasite gene diversity.
Area of Science:
- Malariology
- Parasitology
- Genetics
Background:
- The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, encoded by var genes, are highly polymorphic variant surface antigens critical in malaria pathogenesis.
- Certain PfEMP1 variants binding chondroitin sulfate A (CSA) are implicated in pregnancy malaria.
Purpose of the Study:
- To investigate the conservation of a CSA-binding PfEMP1 variant across global Plasmodium falciparum isolates.
- To analyze the expression of this conserved var gene in placental parasites from Malawian women.
Main Methods:
- Bioinformatic analysis of var gene sequences from global P. falciparum isolates.
- Analysis of var gene expression in placental blood samples from primigravid women in Malawi.
Main Results:
- An unexpected finding of high conservation for a CSA-binding PfEMP1 variant across worldwide P. falciparum isolates.
- N-terminal domains of this PfEMP1 variant showed high conservation, while the CSA-binding domain was more variable.
- Analysis did not support the conserved gene's role in placental infection but identified another common var gene.
Conclusions:
- Reevaluation of assumptions regarding minimal overlap in var gene repertoires between different parasite isolates is necessary.
- The global conservation of specific PfEMP1 variants warrants further study into their broader roles in malaria.
- Understanding var gene repertoire diversity is crucial for developing effective malaria control strategies.