VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.
Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antig...
Guardado en:
| Autores principales: | , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/4bb28a11c9f74b0ca9228dadef771ec6 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:4bb28a11c9f74b0ca9228dadef771ec6 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:4bb28a11c9f74b0ca9228dadef771ec62021-11-18T09:02:54ZVAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta.1932-620310.1371/journal.pone.0069753https://doaj.org/article/4bb28a11c9f74b0ca9228dadef771ec62013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23936092/?tool=EBIhttps://doaj.org/toc/1932-6203Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria.Eduard Rovira-VallbonaIsadora MonteiroAzucena BardajíElisa Serra-CasasDaniel E NeafseyDiana QuelhasClarissa ValimPedro AlonsoCarlota DobañoJaume OrdiClara MenéndezAlfredo MayorPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69753 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Eduard Rovira-Vallbona Isadora Monteiro Azucena Bardají Elisa Serra-Casas Daniel E Neafsey Diana Quelhas Clarissa Valim Pedro Alonso Carlota Dobaño Jaume Ordi Clara Menéndez Alfredo Mayor VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| description |
Plasmodium falciparum infected erythrocytes (IE) accumulate in the placenta through the interaction between Duffy-binding like (DBL) domains of parasite-encoded ligand VAR2CSA and chondroitin sulphate-A (CSA) receptor. Polymorphisms in these domains, including DBL2X and DBL3X, may affect their antigenicity or CSA-binding affinity, eventually increasing parasitemia and its adverse effects on pregnancy outcomes. A total of 373 DBL2X and 328 DBL3X sequences were obtained from transcripts of 20 placental isolates infecting Mozambican women, resulting in 176 DBL2X and 191 DBL3X unique sequences at the protein level. Sequence alignments were divided in segments containing combinations of correlated polymorphisms and the association of segment sequences with placental parasite density was tested using Bonferroni corrected regression models, taking into consideration the weight of each sequence in the infection. Three DBL2X and three DBL3X segments contained signatures of high parasite density (P<0.003) that were highly prevalent in the parasite population (49-91%). Identified regions included a flexible loop that contributes to DBL3X-CSA interaction and two DBL3X motifs with evidence of positive natural selection. Limited antibody responses against signatures of high parasite density among malaria-exposed pregnant women could not explain the increased placental parasitemia. These results suggest that a higher binding efficiency to CSA rather than reduced antigenicity might provide a biological advantage to parasites with high parasite density signatures in VAR2CSA. Sequences contributing to high parasitemia may be critical for the functional characterization of VAR2CSA and the development of tools against placental malaria. |
| format |
article |
| author |
Eduard Rovira-Vallbona Isadora Monteiro Azucena Bardají Elisa Serra-Casas Daniel E Neafsey Diana Quelhas Clarissa Valim Pedro Alonso Carlota Dobaño Jaume Ordi Clara Menéndez Alfredo Mayor |
| author_facet |
Eduard Rovira-Vallbona Isadora Monteiro Azucena Bardají Elisa Serra-Casas Daniel E Neafsey Diana Quelhas Clarissa Valim Pedro Alonso Carlota Dobaño Jaume Ordi Clara Menéndez Alfredo Mayor |
| author_sort |
Eduard Rovira-Vallbona |
| title |
VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| title_short |
VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| title_full |
VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| title_fullStr |
VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| title_full_unstemmed |
VAR2CSA signatures of high Plasmodium falciparum parasitemia in the placenta. |
| title_sort |
var2csa signatures of high plasmodium falciparum parasitemia in the placenta. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/4bb28a11c9f74b0ca9228dadef771ec6 |
| work_keys_str_mv |
AT eduardroviravallbona var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT isadoramonteiro var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT azucenabardaji var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT elisaserracasas var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT danieleneafsey var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT dianaquelhas var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT clarissavalim var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT pedroalonso var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT carlotadobano var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT jaumeordi var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT claramenendez var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta AT alfredomayor var2csasignaturesofhighplasmodiumfalciparumparasitemiaintheplacenta |
| _version_ |
1718420963115139072 |