Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections.


Early, AM; Lievens, M; MacInnis, BL; Ockenhouse, CF; Volkman, SK; Adjei, S; Agbenyega, T; Ansong, D; Gondi, S; Greenwood, B; Hamel, M; Odero, C; Otieno, K; Otieno, W; Owusu-Agyei, S; Asante, KP; Sorgho, H; Tina, L; Tinto, H; Valea, I; Wirth, DF; Neafsey, DE; (2018) Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections. Nature communications, 9 (1). p. 1381. ISSN 2041-1723 DOI: https://doi.org/10.1038/s41467-018-03807-7

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Abstract

Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Disease Control
PubMed ID: 29643376
URI: http://researchonline.lshtm.ac.uk/id/eprint/4647353

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