Variants of<i>Plasmodium falciparum</i>Erythrocyte Membrane Protein 1 Expressed by Different Placental Parasites are Closely Related and Adhere to Chondroitin Sulfate A

Khattab, Ayman; Kun, Jürgen F. J.; Deloron, Philippe; Kremsner, Peter G.; Klinkert, Mo‐Quen

doi:10.1086/319288

Cited by 41 publications

(38 citation statements)

References 15 publications

(22 reference statements)

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“…However, the sequences amplified from gDNAs were different from those amplified from the cDNAs of the same isolates, suggesting that the sequences amplified from the cDNAs were detected because of their abundance. An obvious association between placental isolate cDNA and var2csa was revealed by a phylogenetic analysis that included all of the amplified sequences and all of the PfEMP1 domains previously implicated in pregnancy-associated malaria (6,17,23,29,32,35) (Fig. 2).…”

Section: Resultsmentioning

confidence: 97%

“…S1 in the supplemental material). Four other DBL␥ domains associated with malaria in pregnancy formed small, well-supported clusters: FCR3var.CSA DBL5␥ had at least 70% identity to four sequences from different placental cDNAs; FCR3var.CSA DBL3␥ had Ͼ96% identity with two sequences from different placental isolate cDNAs and one sequence from a child's isolate cDNA; 3D7chr5var DBL3␥ (32), homologous to 720 (23) and var COMMON (42), had Ͼ79% identity with three sequences from different placental cDNAs; and var-CS2 had Ͼ97% identity with the only two sequences amplified from a single placental cDNA.…”

Section: Resultsmentioning

confidence: 99%

“…All but one of the cloned var2csa sequences were identical to the var2csa sequence of the 3D7 isolate within the region that was used as a template for Q-RT-PCR. The var2csa sequence cloned from Mplc78 had a single mismatch of C versus T at nucleotide 11 of the var2csa DBL3x Q-RT-PCR (7,23) are included, and those shown in bold are in the clusters described in the text. Bootstrap values of Ͼ50 are indicated at tree branches leading to clusters of sequences.…”

Section: Resultsmentioning

confidence: 99%

“…Previous nonquantitative studies of the var genes expressed by placental isolates have either used degenerate primers designed to amplify multiple DBL␥ domains or specific primers to amplify DBL domains from some of the three var genes identified as candidate CSA adhesion ligands (15,22,23,32). The amplification of multiple sequences and lack of quantita-tive data prevented the detection of a clear association between a specific var gene and placental sequestration.…”

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confidence: 99%

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Transcribed var Genes Associated with Placental Malaria in MalawianWomen

et al. 2006

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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.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Transcribed var Genes Associated with Placental Malaria in MalawianWomen

et al. 2006

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“…Mothers in their first pregnancy are particularly susceptible to these complications, even if they have preexisting immunity as a result of previous P. falciparum infection. A substantial part of this susceptibility may be attributed to the expression of PfEMP-1 forms that bind placental chondroitin sulfate A (CSA) and are antigenically new to the immune systems of women who have not previously been pregnant (49)(50)(51). Less frequent complications in subsequent pregnancies are thought to be explained by acquired immunity to CSA-binding PfEMP-1 molecules (52,53).…”

Section: Polymorphism Mitigating Placental Inflammation In Malaria Ofmentioning

confidence: 99%

The impact of malaria parasitism: from corpuscles to communities

Wellems¹,

Hayton²,

Fairhurst³

2009

J. Clin. Invest.

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Malaria continues to exert a tremendous health burden on human populations, reflecting astonishingly successful adaptations of the causative Plasmodium parasites. We discuss here how this burden has driven the natural selection of numerous polymorphisms in the genes encoding hemoglobin and other erythrocyte proteins and some effectors of immunity. Plasmodium falciparum, the most deadly parasite species in humans, displays a vigorous system of antigen variation to counter host defenses and families of functionally redundant ligands to invade human cells. Advances in genetics and genomics are providing fresh insights into the nature of these evolutionary adaptations, processes of parasite transmission and infection, and the difficult challenges of malaria control. Evolutionary origin and host preferences of malariacausing parasitesMost cases of malaria in the world are caused by one of the four species of Plasmodium parasites that predominantly infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. Despite efforts over the past century, the global health burden from Plasmodium infections remains approximately 250-600 million episodes of malaria each year in Africa, Asia, Oceania, and Latin America (1, 2). Of these episodes, approximately 40% are caused by P. falciparum, as are nearly all fatalities attributed to malaria.

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