PfEMP1-DBL1alpha amino acid motifs in severe disease states of Plasmodium falciparum malaria.
An infection with Plasmodium falciparum may lead to severe malaria as a result of excessive binding of infected erythrocytes in the microvasculature. Vascular adhesion is mediated by P. falciparum erythrocyte membrane protein-1 (PfEMP1), which is encoded for by highly polymorphic members of the var-gene family. Here, we profile var gene transcription in fresh P. falciparum trophozoites from Ugandan children with malaria through var-specific DBL1alpha-PCR amplification and sequencing. A method for subsectioning region alignments into homology areas (MOTIFF) was developed to examine collected sequences. Specific PfEMP1-DBL1alpha amino acid motifs correlated with rosetting and severe malaria, with motif location corresponding to distinct regions of receptor interaction. The method is potentially applicable to other families of variant proteins and may be useful in identifying sequence-phenotype relationships. The results suggest that certain PfEMP1 sequences are predisposed to inducing severe malaria.
Normark
Johan
J
Department of Microbiology and Tumor and Cell Biology (MTC), Karolinska Institutet and Swedish Institute for Infectious Diseases Control (SMI), Box 280, Nobels väg 16, SE-17177 Stockholm, Sweden.
Nilsson
Daniel
D
Ribacke
Ulf
U
Winter
Gerhard
G
Moll
Kirsten
K
Wheelock
Craig E
CE
Bayarugaba
Justus
J
Kironde
Fred
F
Egwang
Thomas G
TG
Chen
Qijun
Q
Andersson
Björn
B
Wahlgren
Mats
M
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D001665:Binding Sites; D018076:DNA, Complementary / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D016778:Malaria, Falciparum / Q000503:physiopathology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D000953:Antigens, Protozoan; D018076:DNA, Complementary; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum