A conserved Plasmodium protein that localizes to liver stage nuclei is critical for late liver stage development
bioRxiv (Cold Spring Harbor Laboratory)(2022)
Abstract
Malaria, the disease caused by Plasmodium parasites, causes significant mortality and morbidity. Whole parasite vaccination with pre-erythrocytic parasite stages, attenuated through sporozoite irradiation or chemo-attenuation, confers sterilizing immunity against subsequent parasite infection. This provides a rationale for the creation of whole parasite vaccines that are attenuated using gene editing. Here, we report on the creation of a novel genetically attenuated parasite (GAP) by the deletion of Plasmodium LINUP, encoding a liver stage nuclear protein.
Epitope-tagging of LINUP in the rodent malaria parasite Plasmodium yoelii showed LINUP expression exclusively in liver stage nuclei after the onset of exo-erythrocytic schizogony. P. yoelii parasites with a gene deletion of LINUP ( linup —) suffered an exclusive liver stage phenotype with developmental arrested late in exo-erythrocytic schizogony. Liver stages showed incomplete segregation of nuclei and, mitochondria and apicoplast. These cellular perturbations caused a defect in exo-erythrocytic merozoite formation and a concomitant severe attenuation of liver stage-to-blood stage transition. LINUP gene deletion in Plasmodium falciparum also caused a severe defect in late liver stage differentiation. Importantly, P. falciparum linup — liver stages showed a severe defect in parasite transitioning from liver stage to viable blood stage infection. These results suggest that P. falciparum LINUP is a useful target for late liver stage attenuation and an additional gene deletion that can be incorporated into a late liver stage-arresting replication competent whole parasite vaccine.
### Competing Interest Statement
The authors have declared no competing interest.
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Key words
liver stage nuclei,late liver stage development,conserved<i>plasmodium</i>protein
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