Molecular analysis of the cytoadherence phenotype of a Plasmodium falciparum field isolate that binds intercellular adhesion molecule-1.
The ability of Plasmodium falciparum-infected erythrocytes to adhere to endothelial receptors and sequester in diverse host organs is an important pathogenic mechanism. Cytoadherence is mediated by variant surface antigens, which are referred to as PfEMP-1 and are encoded by var genes. The extracellular regions of PfEMP-1 contain multiple conserved cysteine-rich domains that are referred to as Duffy-binding-like (DBL) domains. Here, we analyze the adhesive phenotype of an Indian P. falciparum field isolate, JDP8, which binds ICAM-1 but does not bind CD36. This is a unique cytoadherence phenotype because P. falciparum strains that bind ICAM-1 described thus far usually also bind CD36. Moreover, binding to both receptors is thought to be important for static adhesion under flow. The ICAM-1 binding population of P. falciparum JDP8 adheres to endothelial cells under flow despite poor binding to CD36. We have also identified an expressed var gene, JDP8Icvar, which mediates the ICAM-1 binding phenotype of JDP8. Expression of different regions of JDP8Icvar on the surface of COS-7 cells followed by binding assays demonstrates that the ICAM-1 binding domain maps to the DBL2betaC2 domain of JDP8Icvar. Sequence comparison with two previously identified ICAM-1 binding domains of PfEMP-1, which also map to DBLbetaC2 domains, suggests that diverse P. falciparum isolates use a structurally conserved domain to bind ICAM-1. It thus appears that functional constraints may place limits on the extent of sequence diversity in receptor-binding domains of PfEMP-1.
Chattopadhyay
Rana
R
Malaria Research Group, International Centre for Genetic Engineering and Biotechnology (ICGEB), Aruna Asaf Ali Marg, New Delhi 110067, India.
Taneja
Tarvinder
T
Chakrabarti
Kausik
K
Pillai
C R
CR
Chitnis
Chetan E
CE
D000595:Amino Acid Sequence; D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D016466:CHO Cells; D019556:COS Cells; D002448:Cell Adhesion; D002460:Cell Line; D002522:Chlorocebus aethiops; D006224:Cricetinae; D016054:DNA, Protozoan / Q000737:chemistry / Q000302:isolation & purification; D042783:Endothelial Cells / Q000469:parasitology; D015870:Gene Expression; D017125:Genes, Protozoan; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D011485:Protein Binding; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D018955:CD36 Antigens; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum; D018799:Intercellular Adhesion Molecule-1