ArticleMalaria journal2011
Design of a variant surface antigen-supplemented microarray chip for whole transcriptome analysis of multiple Plasmodium falciparum cytoadherent strains, and identification of strain-transcendent rif and stevor genes.
Article in Malaria journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed.
- Induction of strain-transcending antibodies against Group A PfEMP1 surface antigens from virulent malaria parasites.PLoS pathogens · 2012Trial
- Transcriptomics of Plasmodium vivax rosettingMemorias do Instituto Oswaldo Cruz · 2026Article
- Diamonds in the rif: Alignment-free comparative genomics analysis reveals strain-transcendent Plasmodium falciparum antigens amidst extensive genetic diversity.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2025Article
- Disruption of Parasite hmgb2 Gene Attenuates Plasmodium berghei ANKA Pathogenicity.Infection and immunity · 2015Article
- STEVOR is a Plasmodium falciparum erythrocyte binding protein that mediates merozoite invasion and rosetting.Cell host & microbe · 2014Article
- Comparative Genomics and Systems Biology of Malaria ParasitesCurrent bioinformatics · 2012Article
- A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- New Agilent platform DNA microarrays for transcriptome analysis of Plasmodium falciparum and Plasmodium berghei for the malaria research community.Malaria journal · 2012Article
- Dynamic activation and repression of the plasmodium falciparum rif gene family and their relation to chromatin modification.PloS one · 2012Article
- Module-based subnetwork alignments reveal novel transcriptional regulators in malaria parasite Plasmodium falciparum.BMC systems biology · 2012Article
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6 authors.
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Abstract
backgroundThe cytoadherence of Plasmodium falciparum is thought to be mediated by variant surface antigens (VSA), encoded by var, rif, stevor and pfmc-2tm genes. The last three families have rarely been studied in the context of cytoadherence. As most VSA genes are unique, the variability among sequences has impeded the functional study of VSA across different P. falciparum strains. However, many P. falciparum genomes have recently been sequenced, allowing the development of specific microarray probes for each VSA gene.
methodsAll VSA sequences from the HB3, Dd2 and IT/FCR3 genomes were extracted using HMMer software. Oligonucleotide probes were designed with OligoRankPick and added to the 3D7-based microarray chip. As a proof of concept, IT/R29 parasites were selected for and against rosette formation and the transcriptomes of isogenic rosetting and non-rosetting parasites were compared by microarray.
resultsFrom each parasite strain 50-56 var genes, 125-132 rif genes, 26-33 stevor genes and 3-8 pfmc-2tm genes were identified. Bioinformatic analysis of the new VSA sequences showed that 13 rif genes and five stevor genes were well-conserved across at least three strains (83-100% amino acid identity). The ability of the VSA-supplemented microarray chip to detect cytoadherence-related genes was assessed using P. falciparum clone IT/R29, in which rosetting is known to be mediated by PfEMP1 encoded by ITvar9. Whole transcriptome analysis showed that the most highly up-regulated gene in rosetting parasites was ITvar9 (19 to 429-fold up-regulated over six time points). Only one rif gene (IT4rifA_042) was up-regulated by more than four fold (five fold at 12 hours post-invasion), and no stevor or pfmc-2tm genes were up-regulated by more than two fold. 377 non-VSA genes were differentially expressed by three fold or more in rosetting parasites, although none was as markedly or consistently up-regulated as ITvar9.
conclusionsProbes for the VSA of newly sequenced P. falciparum strains can be added to the 3D7-based microarray chip, allowing the analysis of the entire transcriptome of multiple strains. For the rosetting clone IT/R29, the striking transcriptional upregulation of ITvar9 was confirmed, and the data did not support the involvement of other VSA families in rosette formation.
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