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Published on: December 4, 2015
Transcribed var genes associated with placental malaria in Malawian women
Michael F Duffy1, Aphrodite Caragounis, Rintis Noviyanti
1Department of Medicine (RMH), University of Melbourne, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia. mduffy@unimelb.edu.au
Abstract:
Determining the diversity of PfEMP1 sequences expressed by Plasmodium falciparum-infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBLgamma and var2csa DBL3x domains of PfEMP1 molecules are believed to mediate placental sequestration of infected erythrocytes, so the sequences encoding these domains were amplified from the cDNAs of placental parasites by using degenerate oligonucleotides. The levels of specific var cDNAs were then determined by quantitative reverse transcription-PCR. Homologues of var2csa DBL3x were the predominant sequences amplified from the cDNAs of most placental but not most children's parasites. There was 56% identity between all placental var2csa sequences. Many different DBLgamma domains were amplified from the cDNAs of placental and children's isolates. var2csa transcripts were the most abundant var transcripts of those tested in 11 of 12 placental isolates and 1 of 6 children's isolates. Gravidity did not affect the levels of var2csa transcripts. We concluded that placental malaria is frequently associated with transcription of var2csa but that other var genes are also expressed, and parasites expressing high levels of var2csa are not restricted to pregnant women. The diversity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy.
Insights
Understanding placental malaria requires studying Plasmodium falciparum erythrocyte protein 1 (PfEMP1) sequences. Research shows var2csa is common in placental infections, crucial for pregnancy-specific malaria vaccine development.
Area of Science:
- Immunology
- Parasitology
- Vaccinology
Background:
- Pregnancy malaria, caused by Plasmodium falciparum, poses risks to both mother and child.
- Plasmodium falciparum erythrocyte protein 1 (PfEMP1) mediates infected erythrocyte sequestration in the placenta.
- Understanding PfEMP1 sequence diversity is key for developing effective pregnancy-specific malaria vaccines.
Purpose of the Study:
- To determine the diversity of PfEMP1 sequences in Plasmodium falciparum-infected erythrocytes from placental tissue.
- To investigate the expression levels of specific var gene domains, particularly var2csa and DBLgamma, in placental malaria.
- To assess the correlation between var2csa transcript levels and gravidity.
Main Methods:
- Amplification of DBLgamma and var2csa DBL3x domains from placental parasite cDNAs using degenerate oligonucleotides.
- Quantitative reverse transcription-PCR to determine the levels of specific var cDNAs.
- Sequence identity analysis of amplified var2csa domains.
Main Results:
- Homologues of var2csa DBL3x were predominant in placental parasite isolates but not typically in children's isolates.
- Significant sequence identity (56%) was observed among placental var2csa sequences.
- var2csa transcripts were the most abundant var transcripts in most placental isolates tested.
- DBLgamma domains showed considerable diversity in both placental and children's isolates.
- High var2csa expression was not restricted to pregnant women, and gravidity did not affect transcript levels.
Conclusions:
- Placental malaria is often associated with the transcription of var2csa, a key PfEMP1 domain.
- While var2csa is prevalent, other var genes are also expressed in placental infections.
- The diversity within var2csa sequences is important for understanding immunity and for malaria vaccine development targeting pregnancy.
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