Positive selection of Plasmodium falciparum parasites with multiple var2csa-type PfEMP1 genes during the course of infection in pregnant women

TY - JOUR

T1 - Positive selection of Plasmodium falciparum parasites with multiple var2csa-type PfEMP1 genes during the course of infection in pregnant women

AU - Sander, Adam F

AU - Salanti, Ali

AU - Lavstsen, Thomas

AU - Nielsen, Morten A

AU - Theander, Thor G

AU - Leke, Rose G F

AU - Lo, Yeung Y

AU - Bobbili, Naveen

AU - Arnot, David E

AU - Taylor, Diane W

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Placental malaria infections are caused by Plasmodium falciparum-infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses.

AB - Placental malaria infections are caused by Plasmodium falciparum-infected red blood cells sequestering in the placenta by binding to chondroitin sulfate A, mediated by VAR2CSA, a variant of the PfEMP1 family of adhesion antigens. Recent studies have shown that many P. falciparum genomes have multiple genes coding for different VAR2CSA proteins, and parasites with >1 var2csa gene appear to be more common in pregnant women with placental malaria than in nonpregnant individuals. We present evidence that, in pregnant women, parasites containing multiple var2csa-type genes possess a selective advantage over parasites with a single var2csa gene. Accumulation of parasites with multiple copies of the var2csa gene during the course of pregnancy was also correlated with the development of antibodies involved in blocking VAR2CSA adhesion. The data suggest that multiplicity of var2csa-type genes enables P. falciparum parasites to persist for a longer period of time during placental infections, probably because of their greater capacity for antigenic variation and evasion of variant-specific immune responses.

U2 - 10.1093/infdis/jir168

DO - 10.1093/infdis/jir168

M3 - Journal article

C2 - 21592998

SN - 0022-1899

VL - 203

SP - 1679

EP - 1685

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 11

ER -