Broad analysis reveals a consistent pattern of var gene transcription in Plasmodium falciparum repeatedly selected for a defined adhesion phenotype
Open accessAbstract
Transcription of the majority of the members of the Plasmodium falciparum var multigene family were analysed in two isolates by a quantitative approach. Both of these isolates had been repeatedly selected for adhesion to chondroitin sulphate A (CSA) and one had also been selected for adhesion to hyaluronic acid (HA). These adhesion phenotypes are expressed by many parasites isolated from placentae and are associated with malaria disease in pregnancy. Increased transcription of the var gene var2csa, or its homologue IT4 var4, was associated with the CSA and HA adhesion phenotypes in all parasites suggesting that it was the dominant, if not the only, var gene that encoded adhesion to CSA in these allogeneic isolates. Some var genes were consistently transcribed at higher levels than others regardless of expressed adhesion phenotypes suggesting a transcriptional hierarchy. Unspliced or partial transcripts were detected for most var genes tested. These atypical var gene transcripts may have implications for the regulation of var gene transcription.
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VAR2CSA, the PfEMP1 protein encoded by the var2csa gene, has been identified as the VSA involved in PAM.
“VAR2CSA, the PfEMP1 protein encoded by the var2csa gene, has then been identified as the VSA involved in PAM (Salanti et al. , 2003; Tuikue Ndam et al. , 2005; Duffy et al. , 2005; Duffy et al. , 2006).”
From Towards a vaccine against pregnancy-associated malaria (2008) · cites this paper as Duffy et al., 2005
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Adherence of <i>Plasmodium falciparum</i> to Chondroitin Sulfate A in the Human Placenta
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Evidence for the Involvement of VAR2CSA in Pregnancy-associated Malaria
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Malaria in pregnancy: pathogenesis and immunity
Rogerson, S. J., Hviid, L., Duffy, P. E., Leke, R. F., & Taylor, D. W. (2007) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(07)70022-1 · Cited by 628 · see citing works
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Dynamics of Anti‐VAR2CSA Immunoglobulin G Response in a Cohort of Senegalese Pregnant Women
Tuikue Ndam, N. G., Salanti, A., Le‐Hesran, J. ‐., Cottrell, G., Fievet, N., Turner, L., Sow, S., Dangou, J. ‐., Theander, T., & Deloron, P. (2006) · The Journal of Infectious Diseases · doi:10.1086/500146 · Cited by 89 · see citing works
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Var2CSA minimal CSA binding region is located within the N-terminal region
Srivastava, A., Gangnard, S., Dechavanne, S., Amirat, F., Lewit Bentley, A., Bentley, G. A., & Gamain, B. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020270 · Cited by 76 · see citing works
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Plasmodium falciparum transcriptome analysis reveals pregnancy malaria associated gene expression
Tuikue Ndam, N., Bischoff, E., Proux, C., Lavstsen, T., Salanti, A., Guitard, J., Nielsen, M. A., Coppée, J.-Y., Gaye, A., Theander, T., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0001855 · Cited by 48 · see citing works
Brolin, K. J. M., Persson, K. E. M., Wahlgren, M., Rogerson, S. J., & Chen, Q. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009230 · Cited by 24 · see citing works
“VAR2CSA DBL-Domains Are Recognized by Immune Sera from Pregnant Adults We used flow cytometry to measure antibody levels in a panel of sera from Malawian pregnant women to the variant surface antigens (VSA) of P. falciparum VAR2CSA expressing lab isolate CS2 [32] (figure 1A and figure S1).”
BackgroundInfluentialSelf-citationTowards a vaccine against pregnancy-associated malaria
Tuikue Ndam, N., & Deloron, P. (2008) · Parasite · doi:10.1051/parasite/2008153515 · Cited by 14 · see citing works
Iyamu, U., Vinals, D. F., Tornyigah, B., Arango, E., Bhat, R., Adra, T. R., Grewal, S., Martin, K., Maestre, A., Overduin, M., et al. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1202276 · Cited by 7 · see citing works
- Authors
- Duffy, M. F., Byrne, T. J., Elliott, S. R., Wilson, D. W., Rogerson, S. J., Beeson, J. G., Noviyanti, R., & Brown, G. V.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Walter and Eliza Hall Institute of Medical Research (AU)
- Eijkman Institute for Molecular Biology (ID)
- Corresponding author
- Duffy, Michael F.
- ORCID
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2005-03-15
- Volume
- 56
- Issue
- 3
- Pages
- 774-788
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1934195635
- Cited by
- 93
- References
- 3
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2021: 6 · 2018: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 16.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Funders
- Australian Agency for International Development
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- Plasmodium falciparum, VAR2CSA, malaria in pregnancy, transcriptional hierarchy, unspliced transcripts, gene expression regulation
- MeSH terms
- Animals, Cattle, Cell Adhesion, Chondroitin Sulfates, Female, Gene Expression Regulation, Genes, Dominant, Multigene Family, Hyaluronic Acid, Phenotype, Placenta, Plasmodium falciparum, Pregnancy, Transcription, Genetic, Genetic Variation, Protozoan Proteins, Malaria, Falciparum, Alternative Splicing, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis
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