Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed

Ramesh Subramani; Katharina Quadt; Anine Engholm Jeppesen; Casper Hempel; Jens Emil Vang Petersen; Tue Hassenkam; Lars Hviid; Lea Klingenberg Barfod

doi:10.1128/mBio.01456-15

Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed

Ramesh Subramani, Katharina Quadt, Anine Engholm Jeppesen, Casper Hempel, Jens Emil Vang Petersen, Tue Hassenkam, Lars Hviid, Lea Klingenberg Barfod

17 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	e01456-15
Tidsskrift	mBio
Vol/bind	6
Udgave nummer	5
Antal sider	7
ISSN	2150-7511
DOI	https://doi.org/10.1128/mBio.01456-15
Status	Udgivet - 2015

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10.1128/mBio.01456-15Licens: CC BY-NC-SA

Subramani.mBio 2015Forlagets udgivne version, 1,39 MBLicens: CC BY-NC-SA

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title = "Plasmodium falciparum-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 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.",

author = "Ramesh Subramani and Katharina Quadt and Jeppesen, {Anine Engholm} and Casper Hempel and Petersen, {Jens Emil Vang} and Tue Hassenkam and Lars Hviid and Barfod, {Lea Klingenberg}",

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doi = "10.1128/mBio.01456-15",

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T1 - Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed

AU - Subramani, Ramesh

AU - Quadt, Katharina

AU - Jeppesen, Anine Engholm

AU - Hempel, Casper

AU - Petersen, Jens Emil Vang

AU - Hassenkam, Tue

AU - Hviid, Lars

AU - Barfod, Lea Klingenberg

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1128/mBio.01456-15

DO - 10.1128/mBio.01456-15

M3 - Journal article

C2 - 26443460

SN - 2161-2129

VL - 6

JO - mBio

JF - mBio

IS - 5

M1 - e01456-15

ER -

Plasmodium falciparum-infected erythrocyte knob density is linked to the PfEMP1 variant expressed

Abstract

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