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Differential var gene expression in the organs of patients dying of falciparum malaria.

Montgomery J, Mphande FA, Berriman M, Pain A, Rogerson SJ, Taylor TE, Molyneux ME, Craig A - Mol. Microbiol. (2007)

Bottom Line: Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients.These major var types differed between organs.However, identical var types were expressed in the brains of multiple patients from a single malaria season.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool-Wellcome Programme of Clinical Tropical Research, College of Medicine, Blantyre, Malawi. jmontgomery@mlw.medcol.mw

ABSTRACT
Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis.

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Frequency of sequence groups in var transcripts from the organs of paediatric malaria patients. Shading represents the sequence groups as identified by Bull et al. (2005), which are characterized by the number of cysteine residues and other semi-conserved motifs known as positions of limited variance. The data are expressed as the percentage of var types within each organ containing the corresponding sequence motifs. Brn, brain; Lng, lung; Hrt, heart; Spl, spleen.
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fig02: Frequency of sequence groups in var transcripts from the organs of paediatric malaria patients. Shading represents the sequence groups as identified by Bull et al. (2005), which are characterized by the number of cysteine residues and other semi-conserved motifs known as positions of limited variance. The data are expressed as the percentage of var types within each organ containing the corresponding sequence motifs. Brn, brain; Lng, lung; Hrt, heart; Spl, spleen.

Mentions: Figure 2 shows the distribution of PoLV groups in our var sequences. None of the groups shows an association with the site of sequestration, even when adjusted for the frequency of cloning (data not shown). Expression levels of PoLV group 1 sequences were found to be negatively associated with the variant antibody repertoire in P. falciparum-infected Kenyan children (Bull et al., 2005). These sequences were found at low frequency in our data; immune regulation may preclude the expression of var types containing these conserved sequences in paediatric infections in areas of high malaria transmission such as Malawi.


Differential var gene expression in the organs of patients dying of falciparum malaria.

Montgomery J, Mphande FA, Berriman M, Pain A, Rogerson SJ, Taylor TE, Molyneux ME, Craig A - Mol. Microbiol. (2007)

Frequency of sequence groups in var transcripts from the organs of paediatric malaria patients. Shading represents the sequence groups as identified by Bull et al. (2005), which are characterized by the number of cysteine residues and other semi-conserved motifs known as positions of limited variance. The data are expressed as the percentage of var types within each organ containing the corresponding sequence motifs. Brn, brain; Lng, lung; Hrt, heart; Spl, spleen.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2170262&req=5

fig02: Frequency of sequence groups in var transcripts from the organs of paediatric malaria patients. Shading represents the sequence groups as identified by Bull et al. (2005), which are characterized by the number of cysteine residues and other semi-conserved motifs known as positions of limited variance. The data are expressed as the percentage of var types within each organ containing the corresponding sequence motifs. Brn, brain; Lng, lung; Hrt, heart; Spl, spleen.
Mentions: Figure 2 shows the distribution of PoLV groups in our var sequences. None of the groups shows an association with the site of sequestration, even when adjusted for the frequency of cloning (data not shown). Expression levels of PoLV group 1 sequences were found to be negatively associated with the variant antibody repertoire in P. falciparum-infected Kenyan children (Bull et al., 2005). These sequences were found at low frequency in our data; immune regulation may preclude the expression of var types containing these conserved sequences in paediatric infections in areas of high malaria transmission such as Malawi.

Bottom Line: Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients.These major var types differed between organs.However, identical var types were expressed in the brains of multiple patients from a single malaria season.

View Article: PubMed Central - PubMed

Affiliation: Malawi-Liverpool-Wellcome Programme of Clinical Tropical Research, College of Medicine, Blantyre, Malawi. jmontgomery@mlw.medcol.mw

ABSTRACT
Sequestration of parasitized erythrocytes in the microcirculation of tissues is thought to be important in the pathogenesis of severe falciparum malaria. A major variant surface antigen, var/Plasmodium falciparum erythrocyte membrane protein 1, expressed on the surface of the infected erythrocyte, mediates cytoadherence to vascular endothelium. To address the question of tissue-specific accumulation of variant types, we used the unique resource generated by the clinicopathological study of fatal paediatric malaria in Blantyre, Malawi, to analyse var gene transcription in patients dying with falciparum malaria. Despite up to 102 different var genes being expressed by P. falciparum populations in a single host, only one to two of these genes were expressed at high levels in the brains and hearts of these patients. These major var types differed between organs. However, identical var types were expressed in the brains of multiple patients from a single malaria season. These results provide the first evidence of organ-specific accumulation of P. falciparum variant types and suggest that parasitized erythrocytes can exhibit preferential binding in the body, supporting the hypothesis of cytoadherence-linked pathogenesis.

Show MeSH
Related in: MedlinePlus