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Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing

Natharinee Horata1, Thareerat Kalambaheti, Alister Craig

  • 1Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. h_natharinee@hotmail.com

Malaria Journal
|August 5, 2009
PubMed
Abstract

Insights

This study analyzed Plasmodium falciparum erythrocyte membrane protein 1-DBLalpha (PfEMP1-DBLalpha) sequences from Thai malaria patients. While diverse, specific PfEMP1-DBLalpha features correlate with severe malaria and higher red blood cell rosetting rates.

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Genomics

Background:

  • Rosetting and cytoadherence of Plasmodium falciparum-infected red blood cells are linked to malaria severity.
  • ICAM-1 and CD36 are key host receptors, and PfEMP1-DBLalpha is a major parasite ligand involved in rosette formation.

Purpose of the Study:

  • To investigate if polymorphic PfEMP1-DBLalpha sequences in Thai isolates correlate with rosette formation ability and clinical outcomes in severe vs. uncomplicated malaria.
  • To analyze the association between PfEMP1-DBLalpha sequence variations and malaria severity.

Main Methods:

  • Sequencing and comparative analysis of 295 PfEMP1-DBLalpha sequences from Thai clinical isolates.
  • Network analysis to study sequence relationships.
  • Assessment of parasitized red blood cell binding to host receptors (CD36, ICAM-1 variants).

Main Results:

  • 281 unique amino acid sequences identified, indicating high PfEMP1-DBLalpha diversity.
  • Sequence group 1 (uncomplicated malaria) differed significantly from sequence group 3 (severe malaria).
  • Sequence group 5 exhibited the highest rosetting rate (21.31%); severe malaria isolates in groups 2 and 6 showed significantly higher rosetting rates.

Conclusions:

  • First report on PfEMP1-DBLalpha analysis in Thai clinical isolates using semi-conserved features.
  • PfEMP1-DBLalpha domains are highly diverse in Thai isolates, but common sequences are shared between severe and uncomplicated malaria cases.
  • Specific PfEMP1-DBLalpha features, particularly in cys/PoLV group 5, are associated with high rosetting rates.

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