CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

TY - JOUR

T1 - CD36 selection of 3D7 Plasmodium falciparum associated with severe childhood malaria results in reduced VAR4 expression

AU - Magistrado, Pamela

AU - Staalsoe, Trine

AU - Theander, Thor

AU - Hviid, Lars

AU - Jensen, Anja

PY - 2008

Y1 - 2008

N2 - ABSTRACT: BACKGROUND: A subset of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1SM) is involved in the cytoadherence of P. falciparum-infected red blood cells (iRBC) contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1SM are encoded by group A var genes that are composed of a more constrained range of amino acid sequences than groups B and C var genes encoding PfEMP1UM associated with uncomplicated malaria. Also, unlike var genes from groups B and C, those from group A do not have sequences consistent with CD36 binding - a major cytoadhesion phenotype of P. falciparum isolates. METHODS: A 3D7 PfEMP1SM sub-line (3D7SM) expressing VAR4 (PFD1235w/MAL8P1.207) was selected for binding to CD36. The protein expression of this parasite line was monitored by surface staining of iRBC using VAR4-specific antibodies. The serological phenotype of the 3D7SM parasites was determined by flow cytometry using malaria semi-immune and immune plasma and transcription of the 59 var genes in 3D7 were analysed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using var-specific primers. RESULTS: A selection-induced increased adhesion of 3D7SM iRBC to CD36 resulted in a reduced var4 transcription and VAR4 surface expression. CONCLUSION: VAR4 is not involved in CD36 adhesion. The current findings are consistent with the notion that CD36 adhesion is not associated with particular virulent parasite phenotypes, such as those believed to be exhibited by VAR4 expressing parasites.

AB - ABSTRACT: BACKGROUND: A subset of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1SM) is involved in the cytoadherence of P. falciparum-infected red blood cells (iRBC) contributing to the pathogenesis of severe disease among young children in malaria endemic areas. The PfEMP1SM are encoded by group A var genes that are composed of a more constrained range of amino acid sequences than groups B and C var genes encoding PfEMP1UM associated with uncomplicated malaria. Also, unlike var genes from groups B and C, those from group A do not have sequences consistent with CD36 binding - a major cytoadhesion phenotype of P. falciparum isolates. METHODS: A 3D7 PfEMP1SM sub-line (3D7SM) expressing VAR4 (PFD1235w/MAL8P1.207) was selected for binding to CD36. The protein expression of this parasite line was monitored by surface staining of iRBC using VAR4-specific antibodies. The serological phenotype of the 3D7SM parasites was determined by flow cytometry using malaria semi-immune and immune plasma and transcription of the 59 var genes in 3D7 were analysed by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) using var-specific primers. RESULTS: A selection-induced increased adhesion of 3D7SM iRBC to CD36 resulted in a reduced var4 transcription and VAR4 surface expression. CONCLUSION: VAR4 is not involved in CD36 adhesion. The current findings are consistent with the notion that CD36 adhesion is not associated with particular virulent parasite phenotypes, such as those believed to be exhibited by VAR4 expressing parasites.

U2 - 10.1186/1475-2875-7-204

DO - 10.1186/1475-2875-7-204

M3 - Journal article

C2 - 18844973

SN - 1475-2875

VL - 7

SP - 204

JO - Malaria Journal

JF - Malaria Journal

IS - 1

ER -