Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family.
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have diff...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC3088720?pdf=render |
| _version_ | 1819289352768847872 |
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| author | Joel H Janes Christopher P Wang Emily Levin-Edens Inès Vigan-Womas Micheline Guillotte Martin Melcher Odile Mercereau-Puijalon Joseph D Smith |
| author_facet | Joel H Janes Christopher P Wang Emily Levin-Edens Inès Vigan-Womas Micheline Guillotte Martin Melcher Odile Mercereau-Puijalon Joseph D Smith |
| author_sort | Joel H Janes |
| collection | DOAJ |
| description | The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have different roles in binding and disease. To investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification, we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. By limited dilution cloning, only UpsB and UpsC var genes were isolated, indicating that UpsA var gene expression is rare under in vitro culture conditions. Consequently, three UpsA variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. Binding assays showed that CD36 was the most common adhesion partner of the parasite panel, followed by ICAM-1 and TSP-1, and that CD36 and ICAM-1 binding variants were highly predicted by adhesion domain sequence classification. Binding to other host receptors, including CSA, VCAM-1, HABP1, CD31/PECAM, E-selectin, Endoglin, CHO receptor "X", and Fractalkine, was rare or absent. Our findings identify a category of larger PfEMP1 proteins that are under dual selection for ICAM-1 and CD36 binding. They also support that the UpsA group, in contrast to UpsB and UpsC var genes, has diverged from binding to the major microvasculature receptor CD36 and likely uses other mechanisms to sequester in the microvasculature. These results demonstrate that CD36 and ICAM-1 have left strong signatures of selection on the PfEMP1 family that can be detected by adhesion domain sequence classification and have implications for how this family of proteins is specializing to exploit hosts with varying levels of anti-malaria immunity. |
| first_indexed | 2024-12-24T03:05:29Z |
| format | Article |
| id | doaj.art-b6e5d923273545a9a9d046647aaca645 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-24T03:05:29Z |
| publishDate | 2011-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b6e5d923273545a9a9d046647aaca6452022-12-21T17:18:02ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-05-0175e100203210.1371/journal.ppat.1002032Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family.Joel H JanesChristopher P WangEmily Levin-EdensInès Vigan-WomasMicheline GuillotteMartin MelcherOdile Mercereau-PuijalonJoseph D SmithThe Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family plays a central role in antigenic variation and cytoadhesion of P. falciparum infected erythrocytes. PfEMP1 proteins/var genes are classified into three main subfamilies (UpsA, UpsB, and UpsC) that are hypothesized to have different roles in binding and disease. To investigate whether these subfamilies have diverged in binding specificity and test if binding could be predicted by adhesion domain classification, we generated a panel of 19 parasite lines that primarily expressed a single dominant var transcript and assayed binding against 12 known host receptors. By limited dilution cloning, only UpsB and UpsC var genes were isolated, indicating that UpsA var gene expression is rare under in vitro culture conditions. Consequently, three UpsA variants were obtained by rosette purification and selection with specific monoclonal antibodies to create a more representative panel. Binding assays showed that CD36 was the most common adhesion partner of the parasite panel, followed by ICAM-1 and TSP-1, and that CD36 and ICAM-1 binding variants were highly predicted by adhesion domain sequence classification. Binding to other host receptors, including CSA, VCAM-1, HABP1, CD31/PECAM, E-selectin, Endoglin, CHO receptor "X", and Fractalkine, was rare or absent. Our findings identify a category of larger PfEMP1 proteins that are under dual selection for ICAM-1 and CD36 binding. They also support that the UpsA group, in contrast to UpsB and UpsC var genes, has diverged from binding to the major microvasculature receptor CD36 and likely uses other mechanisms to sequester in the microvasculature. These results demonstrate that CD36 and ICAM-1 have left strong signatures of selection on the PfEMP1 family that can be detected by adhesion domain sequence classification and have implications for how this family of proteins is specializing to exploit hosts with varying levels of anti-malaria immunity.http://europepmc.org/articles/PMC3088720?pdf=render |
| spellingShingle | Joel H Janes Christopher P Wang Emily Levin-Edens Inès Vigan-Womas Micheline Guillotte Martin Melcher Odile Mercereau-Puijalon Joseph D Smith Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. PLoS Pathogens |
| title | Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. |
| title_full | Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. |
| title_fullStr | Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. |
| title_full_unstemmed | Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. |
| title_short | Investigating the host binding signature on the Plasmodium falciparum PfEMP1 protein family. |
| title_sort | investigating the host binding signature on the plasmodium falciparum pfemp1 protein family |
| url | http://europepmc.org/articles/PMC3088720?pdf=render |
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