A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes

ABSTRACT Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human er...

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Autores principales:	Francis B. Ntumngia, Richard Thomson-Luque, Letícia de Menezes Torres, Karthigayan Gunalan, Luzia H. Carvalho, John H. Adams
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e90e9a601934432da28665a351661f75
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spelling	oai:doaj.org-article:e90e9a601934432da28665a351661f752021-11-15T15:50:19ZA Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes10.1128/mBio.01261-162150-7511https://doaj.org/article/e90e9a601934432da28665a351661f752016-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01261-16https://doaj.org/toc/2150-7511ABSTRACT Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human erythrocytes is central to blood-stage infection. Contrary to this established pathway of invasion, there is growing evidence of P. vivax infections occurring in Duffy blood group-negative individuals, suggesting that the parasite might have gained an alternative pathway to infect this group of individuals. Supporting this concept, a second distinct erythrocyte binding protein (EBP2), representing a new member of the DBP family, was discovered in P. vivax and may be the ligand in an alternate invasion pathway. Our study characterizes this novel ligand and determines its potential role in reticulocyte invasion by P. vivax merozoites. EBP2 binds preferentially to young (CD71high) Duffy-positive (Fy+) reticulocytes and has minimal binding capacity for Duffy-negative reticulocytes. Importantly, EBP2 is antigenically distinct from DBP and cannot be functionally inhibited by anti-DBP antibodies. Consequently, our results do not support EBP2 as a ligand for invasion of Duffy-negative blood cells, but instead, EBP2 may represent a novel ligand for an alternate invasion pathway of Duffy-positive reticulocytes. IMPORTANCE For decades, P. vivax infections in humans have been defined by a unique requirement for the interaction between the Duffy binding protein ligand of the parasite and the Duffy blood group antigen receptor (DARC). Recent reports of P. vivax infections in Duffy-negative individuals challenge this paradigm and suggest an alternate pathway of infection, potentially using the recently discovered EBP2. However, we demonstrate that EBP2 host cell specificity is more restricted than DBP binding and that EBP2 binds preferentially to Duffy-positive, young reticulocytes. This finding indicates that this DBP paralog does mediate a Duffy-independent pathway of infection.Francis B. NtumngiaRichard Thomson-LuqueLetícia de Menezes TorresKarthigayan GunalanLuzia H. CarvalhoJohn H. AdamsAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 4 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Francis B. Ntumngia Richard Thomson-Luque Letícia de Menezes Torres Karthigayan Gunalan Luzia H. Carvalho John H. Adams A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
description	ABSTRACT Erythrocyte invasion by malaria parasites is essential for blood-stage development and an important determinant of host range. In Plasmodium vivax, the interaction between the Duffy binding protein (DBP) and its cognate receptor, the Duffy antigen receptor for chemokines (DARC), on human erythrocytes is central to blood-stage infection. Contrary to this established pathway of invasion, there is growing evidence of P. vivax infections occurring in Duffy blood group-negative individuals, suggesting that the parasite might have gained an alternative pathway to infect this group of individuals. Supporting this concept, a second distinct erythrocyte binding protein (EBP2), representing a new member of the DBP family, was discovered in P. vivax and may be the ligand in an alternate invasion pathway. Our study characterizes this novel ligand and determines its potential role in reticulocyte invasion by P. vivax merozoites. EBP2 binds preferentially to young (CD71high) Duffy-positive (Fy+) reticulocytes and has minimal binding capacity for Duffy-negative reticulocytes. Importantly, EBP2 is antigenically distinct from DBP and cannot be functionally inhibited by anti-DBP antibodies. Consequently, our results do not support EBP2 as a ligand for invasion of Duffy-negative blood cells, but instead, EBP2 may represent a novel ligand for an alternate invasion pathway of Duffy-positive reticulocytes. IMPORTANCE For decades, P. vivax infections in humans have been defined by a unique requirement for the interaction between the Duffy binding protein ligand of the parasite and the Duffy blood group antigen receptor (DARC). Recent reports of P. vivax infections in Duffy-negative individuals challenge this paradigm and suggest an alternate pathway of infection, potentially using the recently discovered EBP2. However, we demonstrate that EBP2 host cell specificity is more restricted than DBP binding and that EBP2 binds preferentially to Duffy-positive, young reticulocytes. This finding indicates that this DBP paralog does mediate a Duffy-independent pathway of infection.
format	article
author	Francis B. Ntumngia Richard Thomson-Luque Letícia de Menezes Torres Karthigayan Gunalan Luzia H. Carvalho John H. Adams
author_facet	Francis B. Ntumngia Richard Thomson-Luque Letícia de Menezes Torres Karthigayan Gunalan Luzia H. Carvalho John H. Adams
author_sort	Francis B. Ntumngia
title	A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
title_short	A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
title_full	A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
title_fullStr	A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
title_full_unstemmed	A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes
title_sort	novel erythrocyte binding protein of <named-content content-type="genus-species">plasmodium vivax</named-content> suggests an alternate invasion pathway into duffy-positive reticulocytes
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/e90e9a601934432da28665a351661f75
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A Novel Erythrocyte Binding Protein of <named-content content-type="genus-species">Plasmodium vivax</named-content> Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes

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