<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed

ABSTRACT Members of the clonally variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to vascular receptors. PfEMP1 expression is normally confined to nanoscale knob protrusions on the IE surface membrane. To investigate the rel...

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Autores principales:	Ramesh Subramani, Katharina Quadt, Anine E. Jeppesen, Casper Hempel, Jens Emil Vang Petersen, Tue Hassenkam, Lars Hviid, Lea Barfod
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/692dc9957f444022b5e64fc3503482f2
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spelling	oai:doaj.org-article:692dc9957f444022b5e64fc3503482f22021-11-15T15:41:30Z<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed10.1128/mBio.01456-152150-7511https://doaj.org/article/692dc9957f444022b5e64fc3503482f22015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01456-15https://doaj.org/toc/2150-7511ABSTRACT Members of the clonally variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to vascular receptors. PfEMP1 expression is normally confined to nanoscale knob protrusions on the IE surface membrane. To investigate the relationship between the densities of these IE surface knobs and the PfEMP1 variant expressed, we used specific antibody panning to generate three sublines of the P. falciparum clone IT4, which expresses the PfEMP1 variants IT4VAR04, IT4VAR32b, and IT4VAR60. The knob density in each subline was then determined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) and compared to PfEMP1 and knob-associated histidine-rich protein (KAHRP) expression. Selection for uniform expression of IT4VAR04 produced little change in knob density, compared to unselected IEs. In contrast, selection for IT4VAR32b expression increased knob density approximately 3-fold, whereas IEs selected for IT4VAR60 expression were essentially knobless. When IT4VAR60+ IEs were subsequently selected to express IT4VAR04 or IT4VAR32b, they again displayed low and high knob densities, respectively. All sublines expressed KAHRP regardless of the PfEMP1 expressed. Our study documents for the first time that knob density is related to the PfEMP1 variant expressed. This may reflect topological requirements to ensure optimal adhesive properties of the IEs. IMPORTANCE Infections with Plasmodium falciparum malaria parasites are still responsible for many deaths, especially among children and pregnant women. New interventions are needed to reduce severe illness and deaths caused by this malaria parasite. Thus, a better understanding of the mechanisms behind the pathogenesis is essential. A main reason why Plasmodium falciparum malaria is more severe than disease caused by other malaria species is its ability to express variant antigens on the infected erythrocyte surface. These antigens are presented on membrane protrusions known as knobs. This study set out to investigate the interplay between different variant antigens on the surface of P. falciparum-infected erythrocytes and the density of the knobs on which the antigens are expressed. Such a direct analysis of this relationship has not been reported before but adds to the important understanding of the complexity of malaria antigen presentation.Ramesh SubramaniKatharina QuadtAnine E. JeppesenCasper HempelJens Emil Vang PetersenTue HassenkamLars HviidLea BarfodAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Ramesh Subramani Katharina Quadt Anine E. Jeppesen Casper Hempel Jens Emil Vang Petersen Tue Hassenkam Lars Hviid Lea Barfod <named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
description	ABSTRACT Members of the clonally variant Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediate adhesion of infected erythrocytes (IEs) to vascular receptors. PfEMP1 expression is normally confined to nanoscale knob protrusions on the IE surface membrane. To investigate the relationship between the densities of these IE surface knobs and the PfEMP1 variant expressed, we used specific antibody panning to generate three sublines of the P. falciparum clone IT4, which expresses the PfEMP1 variants IT4VAR04, IT4VAR32b, and IT4VAR60. The knob density in each subline was then determined by atomic force microscopy (AFM) and scanning electron microscopy (SEM) and compared to PfEMP1 and knob-associated histidine-rich protein (KAHRP) expression. Selection for uniform expression of IT4VAR04 produced little change in knob density, compared to unselected IEs. In contrast, selection for IT4VAR32b expression increased knob density approximately 3-fold, whereas IEs selected for IT4VAR60 expression were essentially knobless. When IT4VAR60+ IEs were subsequently selected to express IT4VAR04 or IT4VAR32b, they again displayed low and high knob densities, respectively. All sublines expressed KAHRP regardless of the PfEMP1 expressed. Our study documents for the first time that knob density is related to the PfEMP1 variant expressed. This may reflect topological requirements to ensure optimal adhesive properties of the IEs. IMPORTANCE Infections with Plasmodium falciparum malaria parasites are still responsible for many deaths, especially among children and pregnant women. New interventions are needed to reduce severe illness and deaths caused by this malaria parasite. Thus, a better understanding of the mechanisms behind the pathogenesis is essential. A main reason why Plasmodium falciparum malaria is more severe than disease caused by other malaria species is its ability to express variant antigens on the infected erythrocyte surface. These antigens are presented on membrane protrusions known as knobs. This study set out to investigate the interplay between different variant antigens on the surface of P. falciparum-infected erythrocytes and the density of the knobs on which the antigens are expressed. Such a direct analysis of this relationship has not been reported before but adds to the important understanding of the complexity of malaria antigen presentation.
format	article
author	Ramesh Subramani Katharina Quadt Anine E. Jeppesen Casper Hempel Jens Emil Vang Petersen Tue Hassenkam Lars Hviid Lea Barfod
author_facet	Ramesh Subramani Katharina Quadt Anine E. Jeppesen Casper Hempel Jens Emil Vang Petersen Tue Hassenkam Lars Hviid Lea Barfod
author_sort	Ramesh Subramani
title	<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
title_short	<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
title_full	<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
title_fullStr	<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
title_full_unstemmed	<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed
title_sort	<named-content content-type="genus-species">plasmodium falciparum</named-content>-infected erythrocyte knob density is linked to the pfemp1 variant expressed
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/692dc9957f444022b5e64fc3503482f2
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<named-content content-type="genus-species">Plasmodium falciparum</named-content>-Infected Erythrocyte Knob Density Is Linked to the PfEMP1 Variant Expressed

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