Ectopic Expression of Plasmodium vivax vir Genes in P. falciparum Affects Cytoadhesion via Increased Expression of

Torben Rehn1, Pedro Lubiana1, Thi Huyen Trang Nguyen1

  • 1Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.

Microorganisms
|June 24, 2022
PubMed

Insights

Plasmodium vivax VIR proteins do not directly mediate cytoadhesion in Plasmodium falciparum transfectants. Instead, VIR protein expression induced Plasmodium falciparum erythrocyte binding via PfEMP1 proteins, confounding direct VIR protein function studies.

Area of Science:

  • Malariology
  • Molecular Parasitology
  • Cellular Adhesion

Background:

  • Plasmodium falciparum-infected erythrocytes (PfIEs) adhere to endothelial cell receptors (ECRs) via PfEMP1 proteins, aiding immune evasion.
  • Evidence suggests Plasmodium vivax-infected reticulocytes (PvIRs) also bind ECRs, potentially mediated by VIR proteins.

Purpose of the Study:

  • To investigate the direct involvement of VIR proteins in cytoadhesion using transgenic P. falciparum expressing vir genes.
  • To characterize the localization and function of VIR proteins in infected erythrocyte adhesion.

Main Methods:

  • Generation of P. falciparum transfectants expressing P. vivax vir genes.
  • Analysis of VIR protein localization within infected erythrocytes (Maurer's clefts, erythrocyte membrane).
  • Assessment of binding to endothelial cell receptors (CD36) by transfectants.

Main Results:

  • VIR proteins with transmembrane domains localized to Maurer's clefts and erythrocyte membranes.
  • One transgenic line expressing a non-transmembrane VIR protein (PVX_050690) showed CD36 binding.
  • All CD36-binding transfectants exhibited increased expression of var genes encoding PfEMP1s.
  • Ectopic vir expression appeared to regulate var gene expression, a mechanism yet to be elucidated.

Conclusions:

  • Cytoadhesion observed in P. falciparum expressing vir genes was dependent on PfEMP1, not directly mediated by VIR proteins.
  • The experimental system was unsuitable for characterizing the direct role of VIR proteins in cytoadhesion.
  • Further studies are needed to understand the indirect effect of VIR proteins on var gene expression and cytoadhesion.

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