In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 6 ( 2023-6-29), p. e1011468-
Abstract:
Controlled human malaria infections (CHMI) are a valuable tool to study parasite gene expression in vivo under defined conditions. In previous studies, virulence gene expression was analyzed in samples from volunteers infected with the Plasmodium falciparum (Pf) NF54 isolate, which is of African origin. Here, we provide an in-depth investigation of parasite virulence gene expression in malaria-naïve European volunteers undergoing CHMI with the genetically distinct Pf 7G8 clone, originating in Brazil. Differential expression of var genes, encoding major virulence factors of Pf, PfEMP1s, was assessed in ex vivo parasite samples as well as in parasites from the in vitro cell bank culture that was used to generate the sporozoites (SPZ) for CHMI (Sanaria PfSPZ Challenge (7G8)). We report broad activation of mainly B-type subtelomeric located var genes at the onset of a 7G8 blood stage infection in naïve volunteers, mirroring the NF54 expression study and suggesting that the expression of virulence-associated genes is generally reset during transmission from the mosquito to the human host. However, in 7G8 parasites, we additionally detected a continuously expressed single C-type variant, Pf7G8_040025600, that was most highly expressed in both pre-mosquito cell bank and volunteer samples, suggesting that 7G8, unlike NF54, maintains expression of some previously expressed var variants during transmission. This suggests that in a new host, the parasite may preferentially express the variants that previously allowed successful infection and transmission. Trial registration: ClinicalTrials.gov - NCT02704533 ; 2018-004523-36
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011468
DOI:
10.1371/journal.ppat.1011468.g001
DOI:
10.1371/journal.ppat.1011468.g002
DOI:
10.1371/journal.ppat.1011468.g003
DOI:
10.1371/journal.ppat.1011468.g004
DOI:
10.1371/journal.ppat.1011468.t001
DOI:
10.1371/journal.ppat.1011468.s001
DOI:
10.1371/journal.ppat.1011468.s002
DOI:
10.1371/journal.ppat.1011468.s003
DOI:
10.1371/journal.ppat.1011468.s004
DOI:
10.1371/journal.ppat.1011468.s005
DOI:
10.1371/journal.ppat.1011468.s006
DOI:
10.1371/journal.ppat.1011468.s007
DOI:
10.1371/journal.ppat.1011468.s008
DOI:
10.1371/journal.ppat.1011468.s009
DOI:
10.1371/journal.ppat.1011468.s010
DOI:
10.1371/journal.ppat.1011468.s011
DOI:
10.1371/journal.ppat.1011468.s012
DOI:
10.1371/journal.ppat.1011468.s013
DOI:
10.1371/journal.ppat.1011468.s014
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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