THE CIDR1α-PfEMP1 SEQUENCE FROM INDONESIAN PLASMODIUM FALCIPARUM AND ITS POTENTIAL ASSOCIATION WITH THE CEREBRAL OUTCOME

Erma Sulistyaningsih, Yunita Armiyanti, Rosita Dewi
  MNJ, pp. 34-39  

Abstract


Background: Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is an important protein responsible for the pathogenesis of severe malaria, including cerebral malaria. The protein is highly diverse. The CIDR1α-PfEMP1 binds endothelial protein receptor (EPCR) and may associated with the brain swelling in childhood malaria.

Objective: To analyze the CIDR1α-PfEMP1 from Indonesian isolate and determine its association with cerebral malaria outcome.

Methods: Fifteen blood samples of clinically mild to severe malaria-patient were collected for DNA extraction. Malaria diagnosis was conducted microscopically by Giemsa-stained thin blood smear. The CIDR1α domain was amplified by PCR using specific primer and PCR product was sequenced. The nucleotide sequences were analyzed by NCBI blast, DNASIS MAX 3 and translated into amino acid sequences using Expasy Translation Tool.

Results: One out of fifteen samples was severe malaria case and infected with P.  falciparum, the rest were clinically mild to moderate malaria and infected with pure P. falciparum or mixed infection of P. falciparum and P. vivax. Amplification for CIDR1α domain resulted a single band of + 550 bp from a severe sample only. Sequencing of PCR product on both strands read 524 nucleotides and BLAST analysis confirmed as CIDR1α sequence. Multiple alignment showed 74-78% nucleotide sequence similarity with reference sequences, but amino acid sequences presented 23.5% homologous.

Conclusion: An identified CIDR1α domain only from severe case implicating the potential association with the severe outcome including cerebral malaria, but the highly diverse of the domain needs further studies on the interaction with the pathological-causing receptor in the host.

 


Keywords


Cerebral outcome, CIDR1α, PfEMP1, Plasmodium falciparum

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References


WHO. World Malaria Report. 2019.

Miller LH, Baruch DI, Marsh K DO. The pathogenic basis of malaria. Nature [Internet]; 2002. 415(6872):673–9. Available from: https://pubmed.ncbi.nlm.nih.gov/11832955/

Chen Q, Heddini A, Barragan A, Fernandez V, Pearce SFA, Wahlgren M. The semiconserved head structure of Plasmodium falciparum erythrocyte membrane protein 1 mediates binding to multiple independent host receptors. J Exp Med; 2000. 192(1):1–9. DOI: 10.1084/jem.192.1.1

Magowan C, Wollish W, Anderson L, Leech J. Cytoadherence by Plasmodium Falciparum-infected erythrocytes is correlated with the expression of a family of variable proteins oninfected erythrocytes. J Exp Med; 1988. 168(4):1307–20. DOI: 10.1084/jem.168.4.1307

Smith JD, Subramanian G, Gamain B, Baruch DI ML. Classification of adhesive domains in the Plasmodium falciparum erythrocyte membrane protein 1 family. Mol Biochem Parasitol. 2000;110(2):293–310.

Gardner MJ(1), Hall N, Fung E, White O, Berriman M, Hyman RW, Carlton JM P, A, Nelson KE, Bowman S, Paulsen IT, James K, Eisen JA, Rutherford K S, SL, Craig A, Kyes S, Chan MS, Nene V, Shallom SJ, Suh B, Peterson J AS, Pertea M, Allen J, Selengut J, Haft D, Mather MW, Vaidya AB, Martin DM F, AH, Fraunholz MJ, Roos DS, Ralph SA, McFadden GI, Cummings LM SG, Mungall C, Venter JC, Carucci DJ, Hoffman SL, Newbold C, Davis RW FC, et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature; 2002. 419(6906):498–511

Baruch DI, Ma XC, Singh HB, Bi X, Pasloske BL HR. Identification of a region of PfEMP1 that mediates adherence of Plasmodium falciparum infected erythrocytes to CD36: conserved function with variant sequence. Blood; 1997. 90(9):3766–75. DOI: https://doi.org/10.1182/blood.V90.9.3766

Jespersen JS, Wang CW, Mkumbaye SI, Minja DT, Petersen B, Turner L, et al. Plasmodium falciparum var genes expressed in children with severe malaria encode CIDR α1 domains. EMBO Mol Med; 2016. 8(8):839–50. DOI: 10.15252/emmm.201606188

Kessler A, Dankwa S, Bernabeu M, Harawa V, Danziger SA, Duffy F, et al. cerebral malaria; 2018. 22(5):601–14.

Lau CKY, Turner L, Jespersen JS, Lowe ED, Petersen B, Wang CW, et al. Structural conservation despite huge sequence diversity allows EPCR binding by the pfemp1 family implicated in severe childhood malaria. Cell Host Microbe [Internet]; 2015. 17(1):118–29. DOI: 1016/j.chom.2014.11.007

Degen R, Weiss N BH. Plasmodium falciparum: cloned and expressed CIDR domains of PfEMP1 bind to chondroitin sulfate A. Exp Parasitol; 2000. 95(2):113–21. DOI: 10.1006/expr.2000.4512

WHO. Severe Malaria. Trop Med Int Heal; 2014. 19 (Suppl I): 7–131.

WHO. Gender, health and malaria. Gend Heal; 2007

R R. Women and malaria--special risks and appropriate control strategy. Soc Sci Med; 1993. 37(4):473–80. DOI: https://doi.org/10.1016/0277-9536(93)90282-9

Elyazar IRF, Gething PW, Patil AP, Rogayah H, Kusriastuti R, Wismarini DM, et al. Plasmodium falciparum malaria endemicity in indonesia in 2010. PLoS One; 2011;6(6).

DOI: https://doi.org/10.1371/journal.pone.0021315

Ochola LB, Siddondo BR, Ocholla H, Nkya S, Kimani EN, Williams TN, et al. Specific receptor usage in Plasmodium falciparum cytoadherence is associated with disease outcome. PLoS One; 2011. 6(3):1–9. DOI: https://doi.org/10.1371/journal.pone.0014741

Greenwalt DE, Lipsky RH, Ockenhouse CF, Ikeda H, Tandon NN JG. Membrane glycoprotein CD36: A review of its roles in adherence, signal transduction, and transfusion medicine. Blood; 1992. 80(5):1105–15. Avalaible form: https://pubmed.ncbi.nlm.nih.gov/1381234/

Hsieh FL, Turner L, Bolla JR, Robinson C V., Lavstsen T, Higgins MK. The structural basis for CD36 binding by the malaria parasite. Nat Commun [Internet]; 2016. 7(May):1–11.

DOI: 10.1038/ncomms12837

Turner GDH, Van Chuong L, Mai NTH, Chau TTH, Phu NH, Bethell D, et al. Systemic endothelial activation occurs in both mild and severe malaria: Correlating dermal microvascular endothelial cell phenotype and soluble cell adhesion molecules with disease severity. Am J Pathol; 1998. 152(6):1477–87. Avalaible form: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1858439/


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