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Malaria Journal
Published in: Malaria Journal 1/2009

Open Access 01-12-2009 | Research

Sequence variation of PfEMP1-DBLα in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria

Authors: Natharinee Horata, Thareerat Kalambaheti, Alister Craig, Srisin Khusmith

Published in: Malaria Journal | Issue 1/2009

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Abstract

Background

Rosetting and cytoadherence of Plasmodium falciparum- infected red blood cells have been associated with severity of malaria. ICAM-1 and CD36 are the main host cell receptors, while PfEMP1-DBLα is a major parasite ligand, which can contribute to rosette formation. This study is aimed at demonstrating whether the highly polymorphic PfEMP1-DBLα sequences occurring among Thai isolates causing severe and uncomplicated malaria are associated with their ability to form rosettes and reflected the clinical outcome of the patients.

Methods

Two hundred and ninety five PfEMP1-DBLα sequences from Thai clinical isolates causing severe and uncomplicated malaria were evaluated by sequencing and direct comparison using the specific text string analysis functions in Microsoft Excel and Perl. The relationships between the PfEMP1-DBLα sequences were also analysed by network analysis. The binding abilities of parasitized red blood cells (PRBCs) to CD36, wild type ICAM-1, ICAM-1Kilifi and ICAM-1S22/A under static condition were included.

Results

Two hundred and eighty one non-identical amino acid sequences were identified (< 95% sequence identity). When the distributions of semi-conserved features (PoLV1–4 and sequence group) within the rosetting domain PfEMP1-DBLα were observed, close similarity was found between isolates from the two disease groups. The sequence group 1 representing uncomplicated malaria was significantly different from the sequence group 3 representing the majority of severe malaria (p = 0.027). By using a simple non-phylogenetic approach to visualize the sharing of polymorphic blocks (position specific polymorphic block, PSPB) and cys/PoLV among DBLα sequences, the sequence group 1 was split from the other five sequence groups. The isolates belonging to sequence group 5 gave the highest mean rosetting rate (21.31%). However, within sequence group 2 and group 6, the isolates causing severe malaria had significantly higher rosetting rate than those causing uncomplicated malaria (p = 0.014, p = 0.007, respectively).

Conclusion

This is the first report of PfEMP1-DBLα analysis in clinical Thai isolates using semi-conserved features (cys/PoLV and PSPBs). The cys/PoLV group 5 gave the highest rosetting rate. PfEMP1-DBLα domains in Thai isolates are highly diverse, however, clinical isolates from severe and uncomplicated malaria shared common sequences.
Appendix
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Literature
1.
Chakravorty SJ, Hughes KR, Craig AG: Host response to cytoadherence in Plasmodium falciparum. Biochem Soc Trans. 2008, 36: 221-228. 10.1042/BST0360221.CrossRefPubMed
2.
3.
Berendt AR, Ferguson DJ, Newbold CI: Sequestration in Plasmodium falciparum malaria: sticky cells and sticky problems. Parasitol Today. 1990, 6: 247-254. 10.1016/0169-4758(90)90184-6.CrossRefPubMed
4.
Omi K, Ohashi J, Naka I, Patarapotikul J, Hananantachai H, Looareesuwan S, Tokunaga K: Polymorphisms of CD36 in Thai malaria patients. Southeast Asian J Trop Med Public Health. 2002, 33 (Suppl 3): 1-4.PubMed
5.
Su XZ, Heatwole VM, Wertheimer SP, Guinet F, Herrfeldt JA, Peterson DS, Ravetch JA, Wellems TE: The large diverse gene family var encodes proteins involved in cytoadherence and antigenic variation of Plasmodium falciparum-infected erythrocytes. Cell. 1995, 82: 89-100. 10.1016/0092-8674(95)90055-1.CrossRefPubMed
6.
Leech JH, Barnwell JW, Miller LH, Howard RJ: Identification of a strain-specific malarial antigen exposed on the surface of Plasmodium falciparum-infected erythrocytes. J Exp Med. 1984, 159: 1567-1575. 10.1084/jem.159.6.1567.CrossRefPubMed
7.
Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ: Cloning the P. falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell. 1995, 82: 77-87. 10.1016/0092-8674(95)90054-3.CrossRefPubMed
8.
Newbold C, Warn P, Black G, Berendt A, Craig A, Snow B, Msobo M, Peshu N, Marsh K: Receptor-specific adhesion and clinical disease in Plasmodium falciparum. Am J Trop Med Hyg. 1997, 57: 389-398.PubMed
9.
Rogerson SJ, Tembenu R, Dobano C, Plitt S, Taylor TE, Molyneux ME: Cytoadherence characteristics of Plasmodium falciparum-infected erythrocytes from Malawian children with severe and uncomplicated malaria. Am J Trop Med Hyg. 1999, 61: 467-472.PubMed
10.
Carlson J, Helmby H, Hill AV, Brewster D, Greenwood BM, Wahlgren M: Human cerebral malaria: association with erythrocyte rosetting and lack of anti-rosetting antibodies. Lancet. 1990, 336: 1457-1460. 10.1016/0140-6736(90)93174-N.CrossRefPubMed
11.
Rowe A, Obeiro J, Newbold CI, Marsh K: Plasmodium falciparum rosetting is associated with malaria severity in Kenya. Infect Immun. 1995, 63: 2323-2326.PubMedCentralPubMed
12.
Baruch DI, Rogerson SJ, Cooke BM: Asexual blood stages of malaria antigens: cytoadherence. Chem Immunol. 2002, 80: 144-162. full_text.CrossRefPubMed
13.
Newbold C, Craig A, Kyes S, Rowe A, Fernandez-Reyes D, Fagan T: Cytoadherence, pathogenesis and the infected red cell surface in Plasmodium falciparum. Int J Parasitol. 1999, 29: 927-937. 10.1016/S0020-7519(99)00049-1.CrossRefPubMed
14.
Lindenthal C, Kremsner PG, Klinkert MQ: Commonly recognised Plasmodium falciparum parasites cause cerebral malaria. Parasitol Res. 2003, 91: 363-368. 10.1007/s00436-003-0975-6.CrossRefPubMed
15.
Craig AG, Pinches R, Khan S, Roberts DJ, Turner GD, Newbold CI, Berendt AR: Failure to block adhesion of Plasmodium falciparum-infected erythrocytes to ICAM-1 with soluble ICAM-1. Infect Immun. 1997, 65: 4580-4585.PubMedCentralPubMed
16.
Fernandez-Reyes D, Craig AG, Kyes SA, Peshu N, Snow RW, Berendt AR, Marsh K, Newbold CI: A high frequency African coding polymorphism in the N-terminal domain of ICAM-1 predisposing to cerebral malaria in Kenya. Hum Mol Genet. 1997, 6: 1357-1360. 10.1093/hmg/6.8.1357.CrossRefPubMed
17.
Tse MT, Chakrabarti K, Gray C, Chitnis CE, Craig A: Divergent binding sites on intercellular adhesion molecule-1 (ICAM-1) for variant Plasmodium falciparum isolates. Mol Microbiol. 2004, 51: 1039-1049. 10.1046/j.1365-2958.2003.03895.x.CrossRefPubMed
18.
Gray C, McCormick C, Turner G, Craig A: ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol. 2003, 128: 187-193. 10.1016/S0166-6851(03)00075-6.CrossRefPubMed
19.
Chattopadhyay R, Taneja T, Chakrabarti K, Pillai CR, Chitnis CE: Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1. Mol Biochem Parasitol. 2004, 133: 255-265. 10.1016/j.molbiopara.2003.08.014.CrossRefPubMed
20.
McCormick CJ, Craig A, Roberts D, Newbold CI, Berendt AR: Intercellular adhesion molecule-1 and CD36 synergize to mediate adherence of Plasmodium falciparum-infected erythrocytes to cultured human microvascular endothelial cells. J Clin Invest. 1997, 100: 2521-2529. 10.1172/JCI119794.PubMedCentralCrossRefPubMed
21.
Cooke BM, Berendt AR, Craig AG, MacGregor J, Newbold CI, Nash GB: Rolling and stationary cytoadhesion of red blood cells parasitized by Plasmodium falciparum: separate roles for ICAM-1, CD36 and thrombospondin. Br J Haematol. 1994, 87: 162-170. 10.1111/j.1365-2141.1994.tb04887.x.CrossRefPubMed
22.
Ho M, White NJ: Molecular mechanisms of cytoadherence in malaria. Am J Physiol. 1999, 276: C1231-1242.PubMed
23.
Udomsangpetch R, Reinhardt PH, Schollaardt T, Elliott JF, Kubes P, Ho M: Promiscuity of clinical Plasmodium falciparum isolates for multiple adhesion molecules under flow conditions. J Immunol. 1997, 158: 4358-4364.PubMed
24.
Kun JF, Schmidt-Ott RJ, Lehman LG, Lell B, Luckner D, Greve B, Matousek P, Kremsner PG: Merozoite surface antigen 1 and 2 genotypes and rosetting of Plasmodium falciparum in severe and mild malaria in Lambarene, Gabon. Trans R Soc Trop Med Hyg. 1998, 92: 110-114. 10.1016/S0035-9203(98)90979-8.CrossRefPubMed
25.
Treutiger CJ, Hedlund I, Helmby H, Carlson J, Jepson A, Twumasi P, Kwiatkowski D, Greenwood BM, Wahlgren M: Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria. Am J Trop Med Hyg. 1992, 46: 503-510.PubMed
26.
al-Yaman F, Genton B, Mokela D, Raiko A, Kati S, Rogerson S, Reeder J, Alpers M: Human cerebral malaria: lack of significant association between erythrocyte rosetting and disease severity. Trans R Soc Trop Med Hyg. 1995, 89: 55-58. 10.1016/0035-9203(95)90658-4.CrossRefPubMed
27.
Traore B, Muanza K, Looareesuwan S, Supavej S, Khusmith S, Danis M, Viriyavejakul P, Gay F: Cytoadherence characteristics of Plasmodium falciparum isolates in Thailand using an in vitro human lung endothelial cells model. Am J Trop Med Hyg. 2000, 62: 38-44.PubMed
28.
Angkasekwinai P, Looareesuwan S, Chaiyaroj SC: Lack of significant association between rosette formation and parasitized erythrocyte adherence to purified CD36. Southeast Asian J Trop Med Public Health. 1998, 29: 41-45.PubMed
29.
Ho M, Davis TM, Silamut K, Bunnag D, White NJ: Rosette formation of Plasmodium falciparum-infected erythrocytes from patients with acute malaria. Infect Immun. 1991, 59: 2135-2139.PubMedCentralPubMed
30.
Chotivanich KT, Dondorp AM, White NJ, Peters K, Vreeken J, Kager PA, Udomsangpetch R: The resistance to physiological shear stresses of the erythrocytic rosettes formed by cells infected with Plasmodium falciparum. Ann Trop Med Parasitol. 2000, 94: 219-226. 10.1080/00034980050006384.CrossRefPubMed
31.
Biggs BA, Anders RF, Dillon HE, Davern KM, Martin M, Petersen C, Brown GV: Adherence of infected erythrocytes to venular endothelium selects for antigenic variants of Plasmodium falciparum. J Immunol. 1992, 149: 2047-2054.PubMed
32.
Roberts DJ, Craig AG, Berendt AR, Pinches R, Nash G, Marsh K, Newbold CI: Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature. 1992, 357: 689-692. 10.1038/357689a0.PubMedCentralCrossRefPubMed
33.
Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH: Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell. 1995, 82: 101-110. 10.1016/0092-8674(95)90056-X.PubMedCentralCrossRefPubMed
34.
Treutiger CJ, Heddini A, Fernandez V, Muller WA, Wahlgren M: PECAM-1/CD31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat Med. 1997, 3: 1405-1408. 10.1038/nm1297-1405.CrossRefPubMed
35.
Barnwell JW, Asch AS, Nachman RL, Yamaya M, Aikawa M, Ingravallo P: A human 88-kD membrane glycoprotein (CD36) functions in vitro as a receptor for a cytoadherence ligand on Plasmodium falciparum-infected erythrocytes. J Clin Invest. 1989, 84: 765-772. 10.1172/JCI114234.PubMedCentralCrossRefPubMed
36.
Baruch DI, Ma XC, Singh HB, Bi X, Pasloske BL, Howard RJ: Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood. 1997, 90: 3766-3775.PubMed
37.
Ward CP, Clottey GT, Dorris M, Ji DD, Arnot DE: Analysis of Plasmodium falciparum PfEMP-1/var genes suggests that recombination rearranges constrained sequences. Mol Biochem Parasitol. 1999, 102: 167-177. 10.1016/S0166-6851(99)00106-1.CrossRefPubMed
38.
Kyes S, Taylor H, Craig A, Marsh K, Newbold C: Genomic representation of var gene sequences in Plasmodium falciparum field isolates from different geographic regions. Mol Biochem Parasitol. 1997, 87: 235-238. 10.1016/S0166-6851(97)00071-6.CrossRefPubMed
39.
Fowler EV, Peters JM, Gatton ML, Chen N, Cheng Q: Genetic diversity of the DBLalpha region in Plasmodium falciparum var genes among Asia-Pacific isolates. Mol Biochem Parasitol. 2002, 120: 117-126. 10.1016/S0166-6851(01)00443-1.CrossRefPubMed
40.
Bull PC, Berriman M, Kyes S, Quail MA, Hall N, Kortok MM, Marsh K, Newbold CI: Plasmodium falciparum variant surface antigen expression patterns during malaria. PLoS Pathog. 2005, 1: e26-10.1371/journal.ppat.0010026.PubMedCentralCrossRefPubMed
41.
Rottmann M, Lavstsen T, Mugasa JP, Kaestli M, Jensen AT, Muller D, Theander T, Beck HP: Differential expression of var gene groups is associated with morbidity caused by Plasmodium falciparum infection in Tanzanian children. Infect Immun. 2006, 74: 3904-3911. 10.1128/IAI.02073-05.PubMedCentralCrossRefPubMed
42.
Bull PC, Buckee CO, Kyes S, Kortok MM, Thathy V, Guyah B, Stoute JA, Newbold CI, Marsh K: Plasmodium falciparum antigenic variation. Mapping mosaic var gene sequences onto a network of shared, highly polymorphic sequence blocks. Mol Microbiol. 2008, 68: 1519-1534. 10.1111/j.1365-2958.2008.06248.x.PubMedCentralCrossRefPubMed
43.
Ariey F, Hommel D, Le Scanf C, Duchemin JB, Peneau C, Hulin A, Sarthou JL, Reynes JM, Fandeur T, Mercereau-Puijalon O: Association of severe malaria with a specific Plasmodium falciparum genotype in French Guiana. J Infect Dis. 2001, 184: 237-241. 10.1086/322012.CrossRefPubMed
44.
Kirchgatter K, Portillo Hdel A: Association of severe noncerebral Plasmodium falciparum malaria in Brazil with expressed PfEMP1 DBL1 alpha sequences lacking cysteine residues. Mol Med. 2002, 8: 16-23.PubMedCentralPubMed
45.
Normark J, Nilsson D, Ribacke U, Winter G, Moll K, Wheelock CE, Bayarugaba J, Kironde F, Egwang TG, Chen Q, Andersson B, Wahlgern M: PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 2007, 104: 15835-15840. 10.1073/pnas.0610485104.PubMedCentralCrossRefPubMed
46.
WHO: Severe falciparum malaria. World Health Organization, Communicable Diseases Cluster. Trans R Soc Trop Med Hyg. 2000, 94: S1-90.
47.
Trager W, Jensen JB: Human malaria parasites in continuous culture. Science. 1976, 193: 673-675. 10.1126/science.781840.CrossRefPubMed
48.
Berendt AR, McDowall A, Craig AG, Bates PA, Sternberg MJ, Marsh K, Newbold CI, Hogg N: The binding site on ICAM-1 for Plasmodium falciparum-infected erythrocytes overlaps, but is distinct from, the LFA-1-binding site. Cell. 1992, 68: 71-81. 10.1016/0092-8674(92)90207-S.CrossRefPubMed
49.
Kyes S, Pinches R, Newbold C: A simple RNA analysis method shows var and rif multigene family expression patterns in Plasmodium falciparum. Mol Biochem Parasitol. 2000, 105: 311-315. 10.1016/S0166-6851(99)00193-0.CrossRefPubMed
50.
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
51.
Bull PC, Kyes S, Buckee CO, Montgomery J, Kortok MM, Newbold CI, Marsh K: An approach to classifying sequence tags sampled from Plasmodium falciparum var genes. Mol Biochem Parasitol. 2007, 154: 98-102. 10.1016/j.molbiopara.2007.03.011.PubMedCentralCrossRefPubMed
52.
53.
Smith JD, Craig AG, Kriek N, Hudson-Taylor D, Kyes S, Fagen T, Pinches R, Baruch DI, Newbold CI, Miller LH: Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria. Proc Natl Acad Sci USA. 2000, 97: 1766-1771. 10.1073/pnas.040545897.PubMedCentralCrossRefPubMed
54.
Chaiyaroj SC, Angkasekwinai P, Buranakiti A, Looareesuwan S, Rogerson SJ, Brown GV: Cytoadherence characteristics of Plasmodium falciparum isolates from Thailand: evidence for chondroitin sulfate a as a cytoadherence receptor. Am J Trop Med Hyg. 1996, 55: 76-80.PubMed
55.
Heddini A, Pettersson F, Kai O, Shafi J, Obiero J, Chen Q, Barragan A, Wahlgren M, Marsh K: Fresh isolates from children with severe Plasmodium falciparum malaria bind to multiple receptors. Infect Immun. 2001, 69: 5849-5856. 10.1128/IAI.69.9.5849-5856.2001.PubMedCentralCrossRefPubMed
56.
Kaul DK, Roth EF, Nagel RL, Howard RJ, Handunnetti SM: Rosetting of Plasmodium falciparum-infected red blood cells with uninfected red blood cells enhances microvascular obstruction under flow conditions. Blood. 1991, 78: 812-819.PubMed
57.
Bouharoun-Tayoun H, Oeuvray C, Lunel F, Druilhe P: Mechanisms underlying the monocyte-mediated antibody-dependent killing of Plasmodium falciparum asexual blood stages. J Exp Med. 1995, 182: 409-418. 10.1084/jem.182.2.409.CrossRefPubMed
58.
Miller LH, Baruch DI, Marsh K, Doumbo OK: The pathogenic basis of malaria. Nature. 2002, 415: 673-679. 10.1038/415673a.CrossRefPubMed
59.
Kyriacou HM, Stone GN, Challis RJ, Raza A, Lyke KE, Thera MA, Kone AK, Doumbo OK, Plowe CV, Rowe JA: Differential var gene transcription in Plasmodium falciparum isolates from patients with cerebral malaria compared to hyperparasitaemia. Mol Biochem Parasitol. 2006, 150: 211-218. 10.1016/j.molbiopara.2006.08.005.PubMedCentralCrossRefPubMed
Metadata
Title
Sequence variation of PfEMP1-DBLα in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria
Authors
Natharinee Horata
Thareerat Kalambaheti
Alister Craig
Srisin Khusmith
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2009
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-8-184

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