Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity
Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy bindin...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
Public Library of Science
2020
|
| _version_ | 1797076448944586752 |
|---|---|
| author | Han, J-H Cho, J-S Ong, JJY Park, J-H Nyunt, MH Sutanto, E Trimarsanto, H Petros, B Aseffa, A Getachew, S Sriprawat, K Anstey, NM Grigg, MJ Barber, BE William, T Qi, G Liu, Y Pearson, RD Auburn, S Price, RN Nosten, F Rénia, L Russell, B Han, E-T |
| author_facet | Han, J-H Cho, J-S Ong, JJY Park, J-H Nyunt, MH Sutanto, E Trimarsanto, H Petros, B Aseffa, A Getachew, S Sriprawat, K Anstey, NM Grigg, MJ Barber, BE William, T Qi, G Liu, Y Pearson, RD Auburn, S Price, RN Nosten, F Rénia, L Russell, B Han, E-T |
| author_sort | Han, J-H |
| collection | OXFORD |
| description | Plasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179–479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480–690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate. |
| first_indexed | 2024-03-07T00:03:56Z |
| format | Journal article |
| id | oxford-uuid:76e8ddc8-7f14-4d4b-9d2c-be4db4deb00f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:03:56Z |
| publishDate | 2020 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | oxford-uuid:76e8ddc8-7f14-4d4b-9d2c-be4db4deb00f2022-03-26T20:19:34ZGenetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:76e8ddc8-7f14-4d4b-9d2c-be4db4deb00fEnglishSymplectic ElementsPublic Library of Science 2020Han, J-HCho, J-SOng, JJYPark, J-HNyunt, MHSutanto, ETrimarsanto, HPetros, BAseffa, AGetachew, SSriprawat, KAnstey, NMGrigg, MJBarber, BEWilliam, TQi, GLiu, YPearson, RDAuburn, SPrice, RNNosten, FRénia, LRussell, BHan, E-TPlasmodium vivax is the most widespread and difficult to treat cause of human malaria. The development of vaccines against the blood stages of P. vivax remains a key objective for the control and elimination of vivax malaria. Erythrocyte binding-like (EBL) protein family members such as Duffy binding protein (PvDBP) are of critical importance to erythrocyte invasion and have been the major target for vivax malaria vaccine development. In this study, we focus on another member of EBL protein family, P. vivax erythrocyte binding protein (PvEBP). PvEBP was first identified in Cambodian (C127) field isolates and has subsequently been showed its preferences for binding reticulocytes which is directly inhibited by antibodies. We analysed PvEBP sequence from 316 vivax clinical isolates from eight countries including China (n = 4), Ethiopia (n = 24), Malaysia (n = 53), Myanmar (n = 10), Papua New Guinea (n = 16), Republic of Korea (n = 10), Thailand (n = 174), and Vietnam (n = 25). PvEBP gene exhibited four different phenotypic clusters based on the insertion/deletion (indels) variation. PvEBP-RII (179–479 aa.) showed highest polymorphism similar to other EBL family proteins in various Plasmodium species. Whereas even though PvEBP-RIII-V (480–690 aa.) was the most conserved domain, that showed strong neutral selection pressure for gene purifying with significant population expansion. Antigenicity of both of PvEBP-RII (16.1%) and PvEBP-RIII-V (21.5%) domains were comparatively lower than other P. vivax antigen which expected antigens associated with merozoite invasion. Total IgG recognition level of PvEBP-RII was stronger than PvEBP-RIII-V domain, whereas total IgG inducing level was stronger in PvEBP-RIII-V domain. These results suggest that PvEBP-RII is mainly recognized by natural IgG for innate protection, whereas PvEBP-RIII-V stimulates IgG production activity by B-cell for acquired immunity. Overall, the low antigenicity of both regions in patients with vivax malaria likely reflects genetic polymorphism for strong positive selection in PvEBP-RII and purifying selection in PvEBP-RIII-V domain. These observations pose challenging questions to the selection of EBP and point out the importance of immune pressure and polymorphism required for inclusion of PvEBP as a vaccine candidate. |
| spellingShingle | Han, J-H Cho, J-S Ong, JJY Park, J-H Nyunt, MH Sutanto, E Trimarsanto, H Petros, B Aseffa, A Getachew, S Sriprawat, K Anstey, NM Grigg, MJ Barber, BE William, T Qi, G Liu, Y Pearson, RD Auburn, S Price, RN Nosten, F Rénia, L Russell, B Han, E-T Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title | Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title_full | Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title_fullStr | Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title_full_unstemmed | Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title_short | Genetic diversity and neutral selection in Plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| title_sort | genetic diversity and neutral selection in plasmodium vivax erythrocyte binding protein correlates with patient antigenicity |
| work_keys_str_mv | AT hanjh geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT chojs geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT ongjjy geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT parkjh geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT nyuntmh geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT sutantoe geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT trimarsantoh geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT petrosb geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT aseffaa geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT getachews geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT sriprawatk geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT ansteynm geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT griggmj geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT barberbe geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT williamt geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT qig geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT liuy geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT pearsonrd geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT auburns geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT pricern geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT nostenf geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT renial geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT russellb geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity AT hanet geneticdiversityandneutralselectioninplasmodiumvivaxerythrocytebindingproteincorrelateswithpatientantigenicity |