The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion

Introini, V.; Marin-Menendez, A.; Nettesheim, G.; Lin, Y.-C.; Kariuki, S. N.; Smith, A. L.; Jean, L.; Brewin, J. N.; Rees, D. C.; Cicuta, P.; Rayner, J. C.; Penman, B. S.

doi:10.1101/2022.01.13.476158

bioRxiv · 10.1101/2022.01.13.476158

The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion

Introini, V.·Marin-Menendez, A.·Nettesheim, G.·Lin, Y.-C.·Kariuki, S. N.·Smith, A. L.·Jean, L.·Brewin, J. N.·Rees, D. C.·Cicuta, P.·Rayner, J. C.·Penman, B. S.

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Abstract

Malaria parasites such as Plasmodium falciparum have exerted formidable selective pressures on the human genome. Of the human genetic variants associated with malaria protection, beta thalassaemia (a haemoglobinopathy) was the earliest to be associated with malaria prevalence. However, the malaria protective properties of beta thalassaemic erythrocytes remain unclear. Here we studied the mechanics and surface protein expression of beta thalassaemia heterozygous erythrocytes, measured their susceptibility to P. falciparum invasion, and calculated the energy required for merozoites to invade them. We found invasion-relevant differences in beta thalassaemic cells versus matched controls, specifically: elevated membrane tension, reduced bending modulus, and higher levels of expression of the major invasion receptor basigin. However, these differences acted in opposition to each other with respect to their likely impact on invasion, and overall we did not observe beta thalassaemic cells to have lower P. falciparum invasion efficiency for any of the strains tested.

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Introini, V., Marin-Menendez, A., Nettesheim, G., Lin, Y.-C., Kariuki, S. N., Smith, A. L., Jean, L., Brewin, J. N., Rees, D. C., Cicuta, P., Rayner, J. C., Penman, B. S.. 2022-01-14. The erythrocyte membrane properties of beta thalassaemia heterozygotes and their consequences for Plasmodium falciparum invasion. https://doi.org/10.1101/2022.01.13.476158

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