Malaria's deadly grip: cytoadhesion of Plasmodium falciparum-infected erythrocytes
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Malaria's deadly grip : cytoadhesion of Plasmodium falciparum-infected erythrocytes. / Smith, Joseph D; Rowe, J Alexandra; Higgins, Matthew K; Lavstsen, Thomas.
In: Cellular Microbiology Online, Vol. 15, No. 12, 12.2013, p. 1976-83.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Malaria's deadly grip
T2 - cytoadhesion of Plasmodium falciparum-infected erythrocytes
AU - Smith, Joseph D
AU - Rowe, J Alexandra
AU - Higgins, Matthew K
AU - Lavstsen, Thomas
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2013/12
Y1 - 2013/12
N2 - Cytoadhesion of Plasmodium falciparum-infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed at the infected erythrocyte surface. Although PfEMP1 proteins have extensively diverged under opposing selection pressure to maintain ligand binding while avoiding antibody-mediated detection, recent work has revealed they can be classified into different groups based on chromosome location and domain composition. This grouping reflects functional specialization of PfEMP1 proteins for different human host and microvascular binding niches and appears to be maintained by gene recombination hierarchies. Inone extreme, a specific PfEMP1 variant is associated with placental binding and malaria during pregnancy, while other PfEMP1 subtypes appear to be specialized for infection of malaria naïve hosts. Here, we discuss recent findings on the origins and evolution of the var gene family, the structure-function of PfEMP1 proteins, and a distinct subset of PfEMP1 variants that have been associated with severe childhood malaria.
AB - Cytoadhesion of Plasmodium falciparum-infected erythrocytes to host microvasculature is a key virulence determinant. Parasite binding is mediated by a large family of clonally variant adhesion proteins, termed P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by var genes and expressed at the infected erythrocyte surface. Although PfEMP1 proteins have extensively diverged under opposing selection pressure to maintain ligand binding while avoiding antibody-mediated detection, recent work has revealed they can be classified into different groups based on chromosome location and domain composition. This grouping reflects functional specialization of PfEMP1 proteins for different human host and microvascular binding niches and appears to be maintained by gene recombination hierarchies. Inone extreme, a specific PfEMP1 variant is associated with placental binding and malaria during pregnancy, while other PfEMP1 subtypes appear to be specialized for infection of malaria naïve hosts. Here, we discuss recent findings on the origins and evolution of the var gene family, the structure-function of PfEMP1 proteins, and a distinct subset of PfEMP1 variants that have been associated with severe childhood malaria.
U2 - 10.1111/cmi.12183
DO - 10.1111/cmi.12183
M3 - Journal article
C2 - 23957661
VL - 15
SP - 1976
EP - 1983
JO - Cellular Microbiology
JF - Cellular Microbiology
SN - 1462-5814
IS - 12
ER -
ID: 80786822