Publication: Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria
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2009-08-04
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2009-08-04
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2009
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eng
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1475-2875 (electronic)
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Mahidol University
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BioMed Central
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Horata N, Kalambaheti T, Craig A, Khusmith S. Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria. Malar J. 2009 Aug 4;8:184.
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Natharinee Horata, ณัฐริณี หอระตะ, Thareerat Kalambaheti, ธารีรัตน์ กะลัมพะเหติ, Craig, Alister, Srisin Khusmith, ศรีสิน คูสมิทธิ์ (2009). Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/705.
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Sequence variation of PfEMP1-DBLalpha in association with rosette formation in Plasmodium falciparum isolates causing severe and uncomplicated malaria
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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-DBLalpha is a major parasite ligand,
which can contribute to rosette formation. This study is aimed at demonstrating
whether the highly polymorphic PfEMP1-DBLalpha 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-DBLalpha 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-DBLalpha 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-DBLalpha
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 DBLalpha 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-DBLalpha analysis in clinical Thai
isolates using semi-conserved features (cys/PoLV and PSPBs). The cys/PoLV group 5
gave the highest rosetting rate. PfEMP1-DBLalpha domains in Thai isolates are
highly diverse, however, clinical isolates from severe and uncomplicated malaria
shared common sequences.