bioRxiv · 10.1101/212209
Within-infection diversity of Plasmodium falciparum antigens reflects host-mediated selection
Abstract
Host immunity exerts strong selection on pathogens, but it does not act in a uniform manner across individual hosts. By providing a direct approach for understanding host-specific selection pressures, patterns of intra-host pathogen diversity complement population genetic analyses performed on broad geographic scales. Here, we perform a combined analysis of inter- and intra-host diversity for the malaria parasite Plasmodium falciparum with haplotype sequences of three antigens sampled from over 4,500 natural infections in sub-Saharan Africa using targeted deep sequencing. We find that multi-strain infections in young children contain non-random combinations of parasite genotypes, and identify individual amino acid positions that may contribute to strain-specific blocking of infections. These results demonstrate for the first time that natural host defenses to Plasmodium detectably impact which infections proceed to the blood stage within a given host. This selection partially explains the extreme amino acid diversity observed at many parasite antigens and suggests that vaccines targeting such proteins should account for the impact of allele-specific immunity.
Source connections
Explore related subjects
Keep this discovery
Explore connections, maps & timelines
Early, A. M., Lievens, M., MacInnis, B., Ockenhouse, C. F., Volkman, S. K., RTS,S Clinical Trial Partnership Committee of Inve,, Wirth, D. F., Neafsey, D. E.. 2017-11-01. Within-infection diversity of Plasmodium falciparum antigens reflects host-mediated selection. https://doi.org/10.1101/212209
Cite the original work for its findings. Save a collection to share your selection of sources.