Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

Anja T R Jensen; Pamela Magistrado; Sarah Sharp; Louise Joergensen; Thomas Lavstsen; Antonella Chiucchiuini; Ali Salanti; Lasse S Vestergaard; John P Lusingu; Rob Hermsen; Robert Sauerwein; Jesper Christensen; Morten A Nielsen; Lars Hviid; Colin Sutherland; Trine Staalsoe; Thor G Theander

doi:10.1084/jem.20040274

Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes

Anja T R Jensen, Pamela Magistrado, Sarah Sharp, Louise Joergensen, Thomas Lavstsen, Antonella Chiucchiuini, Ali Salanti, Lasse S Vestergaard, John P Lusingu, Rob Hermsen, Robert Sauerwein, Jesper Christensen, Morten A Nielsen, Lars Hviid, Colin Sutherland, Trine Staalsoe, Thor G Theander

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

Original language	English
Journal	Journal of Experimental Medicine
Volume	199
Issue number	9
Pages (from-to)	1179-90
Number of pages	11
ISSN	0022-1007
DOIs	https://doi.org/10.1084/jem.20040274
Publication status	Published - 2004

Bibliographical note

Keywords: Amino Acid Sequence; Animals; Antibodies, Protozoan; Antigens, Protozoan; Base Sequence; Child; Cloning, Molecular; DNA Primers; Erythrocyte Membrane; Gene Expression Regulation; Genes, Protozoan; Humans; Malaria, Falciparum; Molecular Sequence Data; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic

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Plasmodium falciparum associated with severe childhood malaria preferentially expressess PfEMP1 encoded by group A var genesFinal published version, 375 KB

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Jensen, A. T. R., Magistrado, P., Sharp, S., Joergensen, L., Lavstsen, T., Chiucchiuini, A., Salanti, A., Vestergaard, L. S., Lusingu, J. P., Hermsen, R., Sauerwein, R., Christensen, J., Nielsen, M. A., Hviid, L., Sutherland, C., Staalsoe, T., & Theander, T. G. (2004). Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. Journal of Experimental Medicine, 199(9), 1179-90. https://doi.org/10.1084/jem.20040274

Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. / Jensen, Anja T R; Magistrado, Pamela; Sharp, Sarah; Joergensen, Louise; Lavstsen, Thomas; Chiucchiuini, Antonella; Salanti, Ali; Vestergaard, Lasse S; Lusingu, John P; Hermsen, Rob; Sauerwein, Robert; Christensen, Jesper; Nielsen, Morten A ; Hviid, Lars; Sutherland, Colin; Staalsoe, Trine; Theander, Thor G.

In: Journal of Experimental Medicine, Vol. 199, No. 9, 2004, p. 1179-90.

Research output: Contribution to journal › Journal article › Research › peer-review

Jensen, ATR, Magistrado, P, Sharp, S, Joergensen, L, Lavstsen, T, Chiucchiuini, A, Salanti, A, Vestergaard, LS, Lusingu, JP, Hermsen, R, Sauerwein, R, Christensen, J, Nielsen, MA , Hviid, L, Sutherland, C, Staalsoe, T & Theander, TG 2004, 'Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes', Journal of Experimental Medicine, vol. 199, no. 9, pp. 1179-90. https://doi.org/10.1084/jem.20040274

Jensen, Anja T R ; Magistrado, Pamela ; Sharp, Sarah ; Joergensen, Louise ; Lavstsen, Thomas ; Chiucchiuini, Antonella ; Salanti, Ali ; Vestergaard, Lasse S ; Lusingu, John P ; Hermsen, Rob ; Sauerwein, Robert ; Christensen, Jesper ; Nielsen, Morten A ; Hviid, Lars ; Sutherland, Colin ; Staalsoe, Trine ; Theander, Thor G. / Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes. In: Journal of Experimental Medicine. 2004 ; Vol. 199, No. 9. pp. 1179-90.

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title = "Plasmodium falciparum associated with severe childhood malaria preferentially expresses PfEMP1 encoded by group A var genes",

abstract = "Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.",

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AU - Jensen, Anja T R

AU - Magistrado, Pamela

AU - Sharp, Sarah

AU - Joergensen, Louise

AU - Lavstsen, Thomas

AU - Chiucchiuini, Antonella

AU - Salanti, Ali

AU - Vestergaard, Lasse S

AU - Lusingu, John P

AU - Hermsen, Rob

AU - Sauerwein, Robert

AU - Christensen, Jesper

AU - Nielsen, Morten A

AU - Hviid, Lars

AU - Sutherland, Colin

AU - Staalsoe, Trine

AU - Theander, Thor G

N1 - Keywords: Amino Acid Sequence; Animals; Antibodies, Protozoan; Antigens, Protozoan; Base Sequence; Child; Cloning, Molecular; DNA Primers; Erythrocyte Membrane; Gene Expression Regulation; Genes, Protozoan; Humans; Malaria, Falciparum; Molecular Sequence Data; Plasmodium falciparum; Polymerase Chain Reaction; Protozoan Proteins; Recombinant Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Transcription, Genetic

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N2 - Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

AB - Parasite-encoded variant surface antigens (VSAs) like the var gene-encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSA(SM)) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSA(UM)). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSA(UM) to in vitro-selected sublines expressing VSA(SM) to identify PfEMP1 responsible for the VSA(SM) phenotype. Expression of VSA(SM) was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.

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DO - 10.1084/jem.20040274

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JF - The Journal of Experimental Medicine

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