Ectopic Expression of Plasmodium vivax vir Genes in P. falciparum Affects Cytoadhesion via Increased Expression of Specific var Genes
2022
Rehn, Torben | Lubiana, Pedro | Nguyen, Thi Huyen Trang | Pansegrau, Eva | Schmitt, Marius | Roth, Lisa Katharina | Brehmer, Jana | Röder, Thomas | Cadar, Dániel | Metwally, Nahla Galal | Bruchhaus, Iris
Plasmodium falciparum-infected erythrocytes (PfIEs) adhere to endothelial cell receptors (ECRs) of blood vessels mainly via PfEMP1 proteins to escape elimination via the spleen. Evidence suggests that P. vivax-infected reticulocytes (PvIRs) also bind to ECRs, presumably enabled by VIR proteins, as shown by inhibition experiments and studies with transgenic P. falciparum expressing vir genes. To test this hypothesis, our study investigated the involvement of VIR proteins in cytoadhesion using vir gene-expressing P. falciparum transfectants. Those VIR proteins with a putative transmembrane domain were present in Maurer’s clefts, and some were also present in the erythrocyte membrane. The VIR protein without a transmembrane domain (PVX_050690) was not exported. Five of the transgenic P. falciparum cell lines, including the one expressing PVX_050690, showed binding to CD36. We observed highly increased expression of specific var genes encoding PfEMP1s in all CD36-binding transfectants. These results suggest that ectopic vir expression regulates var expression through a yet unknown mechanism. In conclusion, the observed cytoadhesion of P. falciparum expressing vir genes depended on PfEMP1s, making this experimental unsuitable for characterizing VIR proteins.
显示更多 [+] 显示较少 [-]