Transcription of multiple <i>var</i> genes by individual, trophozoite‐stage <i>Plasmodium falciparum</i> cells expressing a chondroitin sulphate A binding phenotype

Duffy, Michael; Brown, Graham V.; Basuki, Wanny; Krejany, Efrosinia O.; Noviyanti, Rintis; Cowman, Alan F.; Reeder, John C.

doi:10.1046/j.1365-2958.2002.02822.x

Cited by 73 publications

(76 citation statements)

References 31 publications

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“…1b). Using the analysis of Taylor et al (39), these degenerate primers showed a low bias towards amplification of the most frequently detected sequence of Ͻ2% (since 1.02 40 is Ͼ1.5), which is consistent with those of other "universal" DBL domain degenerate primers (8,24,38). Nevertheless, the bias may prevent the amplification of some DBL␥ sequences.…”

Section: Resultssupporting

confidence: 73%

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: Resultssupporting

confidence: 73%

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

et al. 2006

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“…The bestcharacterized VSA, P. falciparum erythrocyte membrane protein 1 (PfEMP1), mediates cytoadherence and antigenic variation (4,41,44). PfEMP1 is encoded by 50 to 60 var genes per haploid parasite genome (15,39,44,45), but only one or a few genes are expressed by each parasite at any given time (12,14,34,45,48). The availability of the complete genome sequence of P. falciparum laboratory clone 3D7 (16) and the ability to select 3D7 for VSA SM -like expression (43) have made it possible to identify the group A var genes likely to code for VSA SM types (21,25,28).…”

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confidence: 99%

Immunoglobulin G Antibody Reactivity to a Group A Plasmodium falciparum Erythrocyte Membrane Protein 1 and Protection from P. falciparum Malaria

et al. 2007

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Variant surface antigens (VSA) on the surface of Plasmodium falciparum-infected red blood cells play a major role in the pathogenesis of malaria and are key targets for acquired immunity. The best-characterized VSA belong to the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family. In areas where P. falciparum is endemic, parasites causing severe malaria and malaria in young children with limited immunity tend to express semiconserved PfEMP1 molecules encoded by group A var genes. Here we investigated antibody responses of Tanzanians who were 0 to 19 years old to PF11_0008, a group A PfEMP1. PF11_0008 has previously been found to be highly transcribed in a nonimmune Dutch volunteer experimentally infected with NF54 parasites. A high proportion of the Tanzanian donors had antibodies against recombinant PF11_0008 domains, and in children who were 4 to 9 years old the presence of antibodies to the PF11_0008 CIDR2␤ domain was associated with reduced numbers of malaria episodes. These results indicate that homologues of PF11_0008 are present in P. falciparum field isolates and suggest that PF11_0008 CIDR2␤-reactive antibodies might be involved in protection against malaria episodes.

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“…Binding to CSA has been localized to DBL␥ domains of these genes (12,18,32,38,43,44). However, recent studies of FCR3varCSA failed to show a correlation between transcription and the CSA adhesion phenotype or specific transcription in placental-type parasites (21,27,35,47). FCR3varCSA (12,50) and varCS2 (43) were originally identified in CSA-adherent parasite lines using reverse transcription PCR (RT-PCR).…”

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confidence: 99%

“…FCR3varCSA (12,50) and varCS2 (43) were originally identified in CSA-adherent parasite lines using reverse transcription PCR (RT-PCR). Since single trophozoites can transcribe multiple var genes simultaneously (21), this approach might detect genes that do not encode the expressed PfEMP1 protein.…”

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confidence: 99%

Cross-Reactive Surface Epitopes on Chondroitin Sulfate A-AdherentPlasmodium falciparum-Infected Erythrocytes Are Associated with Transcription ofvar2csa

et al. 2005

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Malaria in pregnancy is associated with placental accumulation of Plasmodium falciparum-infected erythrocytes (IE) that adhere to chondroitin sulfate A (CSA). Adhesion is mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1), a variant parasite protein expressed on the surface of IE and encoded by var genes. Rabbit antiserum was generated against the CSA-adherent P. falciparum line CS2, in which the dominant var transcribed is var2csa, a relatively conserved var gene that has been associated with CSA adhesion. Anti-CS2 recognized genetically distinct CSA-adherent P. falciparum lines but not CD36-adherent parent lines. Reactivity with anti-CS2 correlated with the level of adhesion to CSA. Fluorescence-activated cell sorting according to binding of anti-CS2 showed reactivity was associated with CSA adhesion and transcription of var2csa. These data are consistent with the hypothesis that var2csa encodes a PfEMP1 expressed on the surface of IE, which mediates adhesion to CSA and is relatively conserved between genetically distinct strains of P. falciparum.

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Transcription of multiple var genes by individual, trophozoite‐stage Plasmodium falciparum cells expressing a chondroitin sulphate A binding phenotype

Cited by 73 publications

References 31 publications

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Transcribed var Genes Associated with Placental Malaria in MalawianWomen

Immunoglobulin G Antibody Reactivity to a Group A Plasmodium falciparum Erythrocyte Membrane Protein 1 and Protection from P. falciparum Malaria

Cross-Reactive Surface Epitopes on Chondroitin Sulfate A-AdherentPlasmodium falciparum-Infected Erythrocytes Are Associated with Transcription ofvar2csa

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