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Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans [ChIP-seq]

ABSTRACT: Clonally variant genes (CVGs) play fundamental roles in the adaptation of Plasmodium falciparum parasites to the fluctuating conditions of the human host, but their expression patterns under the natural conditions of the blood circulation have been characterized in detail only for a few specific gene families. Here we provide a detailed characterization of the full P. falciparum transcriptome across the full intraerythrocytic development cycle (IDC) at the onset of a blood infection in non-immune human volunteers. We found that the vast majority of transcriptional differences between parasites obtained from the volunteers and the parental parasite line maintained in culture occur for CVGs. Specifically, we observed a major increase in the transcript levels of most members of the pfmc-2tm and gbp families and of specific genes of other families, in addition to previously reported changes in var and clag3 genes. The expression patterns were almost identical between parasites obtained from the different volunteers. Large transcriptional differences correlate with changes in the distribution of histone modifications associated with heterochromatin, confirming their epigenetic nature. The analysis of parasites collected at different points along the infection indicates that when parasites pass through transmission stages, the epigenetic memory at CVG loci is lost, resulting in a reset of their expression state and reestablishment of new epigenetic patterns.

ORGANISM(S): Plasmodium falciparum

PROVIDER: GSE166390 | GEO | 2021/07/01

REPOSITORIES: GEO

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Project description:Description: Experimental exposure to malaria parasites can lead to development of protective immunity, providing a foothold for the development of a malaria vaccine. The goal of this study is to investigate immune transcriptional profiles associated with malaria protective immune responses induced by experimental Chemo-Prophylaxis and Sporozoites (CPS) immunization of P. falciparum-naive human volunteers. Samples for this study were obtained from a CPS-immunization study conducted in 2011 (ClinicalTrials.gov Identifier: NCT01218893), where healthy volunteers received CPS-immunization with bites from different numbers of P. falciparum-infected mosquitoes (three times 15 (n=5), 10 (n=9) or 5 (n=10)). Five control subjects received uninfected mosquito bites under chloroquine prophylaxis. Fifteen weeks after discontinuation of chloroquine prophylaxis, all volunteers were challenged by exposure to infected mosquito bites. Study Design: A maximum of 30 volunteers were divided into four groups. All volunteers received weekly chloroquine prophylaxis for a period of 13 weeks (91 days). During these 13 weeks, on days 8, 36 and 64 they were exposed to the bites of 15 mosquitoes. Group 1 (n=5, positive control) received three CPS immunizations by 15 mosquitoes infected with P. falciparum sporozoites. Group 2 (n=10) received three times 10 bites from infected mosquitoes and 5 bites from uninfected mosquitoes. Group 3 (n=10) received three times 5 bites from infected mosquitoes and 10 bites from uninfected mosquitoes. Group 4 (n=5), the negative control, received three placebo immunizations with 15 bites of uninfected mosquitoes. Fifteen weeks after discontinuation of chloroquine prophylaxis, all 30 volunteers were challenged at day 196 by the bites of 5 infectious mosquitoes and followed for 21 days. All subjects were treated with chloroquine 21 days after challenge or whenever they had a positive thick smear during that period.

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Expression patterns of Plasmodium falciparum clonally variant genes at the onset of a blood infection in non-immune humans [ChIP-seq]

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