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Identification of a conserved var gene in different Plasmodium falciparum strains

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season

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  2. Longitudinal analysis of naturally acquired PfEMP1 CIDR domain variant antibodies identifies associations with malaria protection

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  3. Dynamics of PfEMP1 Antibody Profile From Birth to 12 Months of Age in Beninese Infants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Plasmodium falciparum-CD36 Structure-Function Relationships Defined by Ortholog Scanning Mutagenesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Sandra Dimonte
  • Ellen I Bruske
  • Corinna Enderes
  • Thomas D Otto
  • Louise Turner
  • Peter Kremsner
  • Matthias Frank
Vis graf over relationer

BACKGROUND: The multicopy var gene family of Plasmodium falciparum is of crucial importance for pathogenesis and antigenic variation. So far only var2csa, the var gene responsible for placental malaria, was found to be highly conserved among all P. falciparum strains. Here, a new conserved 3D7 var gene (PF3D7_0617400) is identified in several field isolates.

METHODS: DNA sequencing, transcriptional analysis, Cluster of Differentiation (CD) 36-receptor binding, indirect immunofluorescence with PF3D7_0617400-antibodies and quantification of surface reactivity against semi-immune sera were used to characterize an NF54 clone and a Gabonese field isolate clone (MOA C3) transcribing the gene. A population of 714 whole genome sequenced parasites was analysed to characterize the conservation of the locus in African and Asian isolates. The genetic diversity of two var2csa fragments was compared with the genetic diversity of 57 microsatellites fragments in field isolates.

RESULTS: PFGA01_060022400 was identified in a Gabonese parasite isolate (MOA) from a chronic infection and found to be 99% identical with PF3D7_0617400 of the 3D7 genome strain. Transcriptional analysis and immunofluorescence showed expression of the gene in an NF54 and a MOA clone but CD36 binding assays and surface reactivity to semi-immune sera differed markedly in the two clones. Long-read Pacific bioscience whole genome sequencing showed that PFGA01_060022400 is located in the internal cluster of chromosome 6. The full length PFGA01_060022400 was detected in 36 of 714 P. falciparum isolates and 500 bp fragments were identified in more than 100 isolates. var2csa was in parts highly conserved (He = 0) but in other parts as variable (He = 0.86) as the 57 microsatellites markers (He = 0.8).

CONCLUSIONS: Individual var gene sequences exhibit conservation in the global parasite population suggesting that purifying selection may limit overall genetic diversity of some var genes. Notably, field and laboratory isolates expressing the same var gene exhibit markedly different phenotypes.

OriginalsprogEngelsk
TidsskriftMalaria Journal
Vol/bind19
Udgave nummer1
Sider (fra-til)194
ISSN1475-2875
DOI
StatusUdgivet - 29 maj 2020

ID: 62341520