Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Abstract

Determining the diversity of PfEMP1 sequences expressed by Plasmodium falciparum-infected erythrocytes isolated from placentas is important for attempts to develop a pregnancy-specific malaria vaccine. The DBL␥ and var2csa DBL3x domains of PfEMP1 molecules are believed to mediate placental sequestration of infected erythrocytes, so the sequences encoding these domains were amplified from the cDNAs of placental parasites by using degenerate oligonucleotides. The levels of specific var cDNAs were then determined by quantitative reverse transcription-PCR. Homologues of var2csa DBL3x were the predominant sequences amplified from the cDNAs of most placental but not most children's parasites. There was 56% identity between all placental var2csa sequences. Many different DBL␥ domains were amplified from the cDNAs of placental and children's isolates. var2csa transcripts were the most abundant var transcripts of those tested in 11 of 12 placental isolates and 1 of 6 children's isolates. Gravidity did not affect the levels of var2csa transcripts. We concluded that placental malaria is frequently associated with transcription of var2csa but that other var genes are also expressed, and parasites expressing high levels of var2csa are not restricted to pregnant women. The diversity of var2csa sequences may be important for understanding immunity and for the development of vaccines for malaria during pregnancy.

MyD88 Signaling Is Directly Involved in the Development of Murine Placental Malaria

“…It is well established that in humans, accumulation of P. falciparum-iRBCs in the placenta occurs through the adhesion of PfEMP-1 to CSA, leading to malaria pathogenesis during pregnancy (2,5,36). However, this characteristic is not exclusive to P. falciparum.…”

“…During Plasmodium falciparum infection, VAR2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family (5)(6)(7)(8), which interacts with chondroitin sulfate A (CSA) and hyaluronic acid (HA) (9,10), facilitates the sequestration of iRBCs in the placenta. The increased expression of CSA and HA in placental tissue promotes iRBC accumulation and interaction between the parasite and host cells.…”

Antigenic Variation in Plasmodium falciparum : Gene Organization and Regulation of the var Multigene Family

“…VAR2CSA is conserved at approximately 70 to 80% amino acid identity across global isolates (53,87,100) and is transcriptionally upregulated in placental isolates and parasites selected to bind CSA (23,24,39,87,101). Disruption of var2CSA causes infected erythrocytes to lose their ability to bind CSA (25,104).…”

Biology of Malaria Parasites

“…[ 93 ] This phenomenon is not restricted to the placenta in that, there is a dominant expression of particular var genes in the various tissue. [ 94 ] This tissue specific expression of particular var genes implies that different tissues are selecting out different parasite populations based on the particular PfEMPI being expressed on the surface of the infected erythrocyte.…”