Amplification of Duffy binding protein-encoding gene allows Plasmodium vivax to evade host anti-DBP humoral immunity.
Antibodies, Blocking
/ blood
Antibodies, Protozoan
/ blood
Antigens, Protozoan
/ genetics
Duffy Blood-Group System
/ genetics
Erythrocytes
/ parasitology
Gene Dosage
Humans
Immune Evasion
/ genetics
Immunity, Humoral
Malaria, Vivax
/ blood
Plasmodium vivax
/ genetics
Protozoan Proteins
/ genetics
RNA, Messenger
/ metabolism
RNA, Protozoan
/ metabolism
Receptors, Cell Surface
/ genetics
Reticulocytes
/ parasitology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
19 02 2020
19 02 2020
Historique:
received:
08
08
2019
accepted:
18
01
2020
entrez:
21
2
2020
pubmed:
23
2
2020
medline:
30
4
2020
Statut:
epublish
Résumé
Antigenic variation, the capacity to produce a range of variable antigens, is a well-described strategy of Plasmodium and other parasites to evade host immunity. Here, we show that gene amplification is an additional evasion mechanism used by Plasmodium vivax to escape humoral immunity targeting PvDBP, the key ligand involved in reticulocyte invasion. PvDBP gene amplification leads to increased mRNA levels and protects P. vivax in vitro against invasion inhibitory human monoclonal antibodies targeting a conserved binding domain of DBP. Patient samples suggest that parasites with increased pvdbp copy number are able to infect individuals with naturally acquired antibodies highly blocking the binding of PvDBP to the Duffy receptor. These results show that gene copy number variation affect the parasite's ability to evade anti-PvDBP humoral immunity.
Identifiants
pubmed: 32075983
doi: 10.1038/s41467-020-14574-9
pii: 10.1038/s41467-020-14574-9
pmc: PMC7031336
doi:
Substances chimiques
ACKR1 protein, human
0
Antibodies, Blocking
0
Antibodies, Protozoan
0
Antigens, Protozoan
0
Duffy Blood-Group System
0
Duffy antigen binding protein, Plasmodium
0
Protozoan Proteins
0
RNA, Messenger
0
RNA, Protozoan
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
953Subventions
Organisme : NIAID NIH HHS
ID : U19 AI129392
Pays : United States
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