Skip to main content
Top
Published in: Malaria Journal 1/2003

Open Access 01-12-2003 | Research

Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires

Authors: Adriana Tami, Rosalynn Ord, Geoffrey AT Targett, Colin J Sutherland

Published in: Malaria Journal | Issue 1/2003

Login to get access

Abstract

Background

The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires.

Methods

Distinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-α domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-α of known location in the 3D7 genome.

Results

Sympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci.

Conclusion

The parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.
Appendix
Available only for authorised users
Literature
1.
go back to reference Su X-Z, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE: A large and diverse gene family (var) encodes 250–300 kD proteins implicated in the antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes. Cell. 1995, 82: 89-100.CrossRefPubMed Su X-Z, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE: A large and diverse gene family (var) encodes 250–300 kD proteins implicated in the antigenic variation and cytoadherence of Plasmodium falciparum-infected erythrocytes. Cell. 1995, 82: 89-100.CrossRefPubMed
2.
go back to reference Sutherland CJ: The flip-side of cytoadherence: Immune selection, antigenic variation and the var genes of Plasmodium falciparum. Parasitol Today. 1998, 14: 329-332. 10.1016/S0169-4758(98)01276-9.CrossRefPubMed Sutherland CJ: The flip-side of cytoadherence: Immune selection, antigenic variation and the var genes of Plasmodium falciparum. Parasitol Today. 1998, 14: 329-332. 10.1016/S0169-4758(98)01276-9.CrossRefPubMed
3.
go back to reference Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S: Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002, 419: 498-511. 10.1038/nature01097.CrossRefPubMed Gardner MJ, Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM, Pain A, Nelson KE, Bowman S: Genome sequence of the human malaria parasite Plasmodium falciparum. Nature. 2002, 419: 498-511. 10.1038/nature01097.CrossRefPubMed
4.
go back to reference Taylor HM, Kyes SA, Harris D, Kriek N, Newbold CI: A study of var gene transcription in vitro using universal var gene primers. Mol Biochem Parasitol. 2000, 105: 13-23. 10.1016/S0166-6851(99)00159-0.CrossRefPubMed Taylor HM, Kyes SA, Harris D, Kriek N, Newbold CI: A study of var gene transcription in vitro using universal var gene primers. Mol Biochem Parasitol. 2000, 105: 13-23. 10.1016/S0166-6851(99)00159-0.CrossRefPubMed
5.
go back to reference Taylor HM, Kyes SA, Newbold CI: Var gene diversity is generated by frequent recombination events. Mol Biochem Parasitol. 2000, 110: 391-397. 10.1016/S0166-6851(00)00286-3.CrossRefPubMed Taylor HM, Kyes SA, Newbold CI: Var gene diversity is generated by frequent recombination events. Mol Biochem Parasitol. 2000, 110: 391-397. 10.1016/S0166-6851(00)00286-3.CrossRefPubMed
6.
go back to reference Kirchgatter K, Mosbach R, del Portillo HA: Plasmodium falciparum : DBL-1 var sequence analysis in field isolates from Central Brazil. Exp Parasitol. 2000, 95: 154-157. 10.1006/expr.2000.4520.CrossRefPubMed Kirchgatter K, Mosbach R, del Portillo HA: Plasmodium falciparum : DBL-1 var sequence analysis in field isolates from Central Brazil. Exp Parasitol. 2000, 95: 154-157. 10.1006/expr.2000.4520.CrossRefPubMed
7.
go back to reference Fowler EV, Peters JM, Gatton ML, Chen N, Cheng Q: Genetic diversity of the DBLα region in P lasmodium falciparum var genes among Asia-Pacific isolates. Mol Biochem Parasitol. 2002, 120: 117-126. 10.1016/S0166-6851(01)00443-1.CrossRefPubMed Fowler EV, Peters JM, Gatton ML, Chen N, Cheng Q: Genetic diversity of the DBLα region in P lasmodium falciparum var genes among Asia-Pacific isolates. Mol Biochem Parasitol. 2002, 120: 117-126. 10.1016/S0166-6851(01)00443-1.CrossRefPubMed
8.
go back to reference Aguir JC, Albrecht GR, Cegielski P, Greenwood BM, Jensen JB, Lallinger G, Martinez A, McGregor IA, Minjas JN, Neequaye J, Patarroyo ME, Sherwood JA, Howard RJ: Agglutination of Plasmodium falciparum-infected erythrocytes from East and West African isolates by human sera from distant geographic regions. Am J Trop Med Hyg. 1992, 47: 621-632. Aguir JC, Albrecht GR, Cegielski P, Greenwood BM, Jensen JB, Lallinger G, Martinez A, McGregor IA, Minjas JN, Neequaye J, Patarroyo ME, Sherwood JA, Howard RJ: Agglutination of Plasmodium falciparum-infected erythrocytes from East and West African isolates by human sera from distant geographic regions. Am J Trop Med Hyg. 1992, 47: 621-632.
9.
go back to reference Giha HA, Theander TG, Staalsoe , Roper C, Elhassan IM, Babiker H, Satti GMH, Arnot DE, Hviid L: Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes. Am J Trop Med Hyg. 1998, 58: 399-405.PubMed Giha HA, Theander TG, Staalsoe , Roper C, Elhassan IM, Babiker H, Satti GMH, Arnot DE, Hviid L: Seasonal variation in agglutination of Plasmodium falciparum-infected erythrocytes. Am J Trop Med Hyg. 1998, 58: 399-405.PubMed
10.
go back to reference Bull PC, Lowe BS, Kortok M, Molyneux CS, Newbold CI, Marsh K: Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nature Med. 1998, 4: 358-360.PubMedCentralCrossRefPubMed Bull PC, Lowe BS, Kortok M, Molyneux CS, Newbold CI, Marsh K: Parasite antigens on the infected red cell surface are targets for naturally acquired immunity to malaria. Nature Med. 1998, 4: 358-360.PubMedCentralCrossRefPubMed
11.
go back to reference Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM, Anderson RM: The maintenance of strain structure in populations of recombining infectious agents. Nature Med. 1996, 2: 437-442.CrossRefPubMed Gupta S, Maiden MCJ, Feavers IM, Nee S, May RM, Anderson RM: The maintenance of strain structure in populations of recombining infectious agents. Nature Med. 1996, 2: 437-442.CrossRefPubMed
12.
go back to reference Tami A, Grundmann H, Sutherland C, McBride JS, Cavanagh DR, Campos E, Snounou G, Barnabe C, Tibayrenc M, Warhurst DC: Restricted genetic and antigenic diversity of Plasmodium falciparum under mesoendemic transmission in the Venezuelan Amazon. Parasitology. 2002, 124: 569-581.CrossRefPubMed Tami A, Grundmann H, Sutherland C, McBride JS, Cavanagh DR, Campos E, Snounou G, Barnabe C, Tibayrenc M, Warhurst DC: Restricted genetic and antigenic diversity of Plasmodium falciparum under mesoendemic transmission in the Venezuelan Amazon. Parasitology. 2002, 124: 569-581.CrossRefPubMed
13.
go back to reference Bland M: In: An Introduction to Medical Statistics. OUP Oxford. 1987, Chapter 6, sect 64: Bland M: In: An Introduction to Medical Statistics. OUP Oxford. 1987, Chapter 6, sect 64:
14.
go back to reference Freitas-Junior LH, Bottius E, Pirrit LA, Deitsch KW, Scheidig C, Guinet F, Nehrbass U, Wellems TE, Scherf A: Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature. 2000, 407: 1018-1022. 10.1038/35039531.CrossRefPubMed Freitas-Junior LH, Bottius E, Pirrit LA, Deitsch KW, Scheidig C, Guinet F, Nehrbass U, Wellems TE, Scherf A: Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature. 2000, 407: 1018-1022. 10.1038/35039531.CrossRefPubMed
15.
go back to reference Vazquez-Macias A, Martinez-Cruz P, Castaneda-Patian MC, Scheidig C, Gysin J, Scherf A, Hernandez-Rivas R: A distinct 5' flanking var gene region regulates Plasmodium falciparum variant erythrocyte surface antigen expression in placental malaria. Mol Microbiol. 2002, 45: 155-167. 10.1046/j.1365-2958.2002.02999.x.CrossRefPubMed Vazquez-Macias A, Martinez-Cruz P, Castaneda-Patian MC, Scheidig C, Gysin J, Scherf A, Hernandez-Rivas R: A distinct 5' flanking var gene region regulates Plasmodium falciparum variant erythrocyte surface antigen expression in placental malaria. Mol Microbiol. 2002, 45: 155-167. 10.1046/j.1365-2958.2002.02999.x.CrossRefPubMed
Metadata
Title
Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires
Authors
Adriana Tami
Rosalynn Ord
Geoffrey AT Targett
Colin J Sutherland
Publication date
01-12-2003
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2003
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-2-7

Other articles of this Issue 1/2003

Malaria Journal 1/2003 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.