Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion

Karen Hayton; Deepak Gaur; Anna Liu; Jonathan Takahashi; Bruce Henschen; Subhash Singh; Lynn Lambert; Tetsuya Furuya; Rachel Bouttenot; Michelle Doll; Fatima Nawaz; Jianbing Mu; Lubin Jiang; Louis H. Miller; Thomas E. Wellems

doi:10.1016/j.chom.2008.06.001

Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion

Karen Hayton, Deepak Gaur, Anna Liu, Jonathan Takahashi, Bruce Henschen, Subhash Singh, Lynn Lambert, Tetsuya Furuya, Rachel Bouttenot, Michelle Doll, Fatima Nawaz, Jianbing Mu, Lubin Jiang, Louis H. Miller, Thomas E. Wellems^*

^*Corresponding author for this work

Medicine, General Medicine Division

Research output: Contribution to journal › Article › peer-review

205 Scopus citations

Abstract

Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors.

Original language	English (US)
Pages (from-to)	40-51
Number of pages	12
Journal	Cell Host and Microbe
Volume	4
Issue number	1
DOIs	https://doi.org/10.1016/j.chom.2008.06.001
State	Published - Jul 17 2008

Funding

We thank Andre Laughinghouse, Kevin Lee, Robert Gwadz, Brian Keegan, Josh Reece, Cheryl Kothe, Mark Szarowicz, Angela Lunger, Kelly Magee, and Carole Long for help with mosquito and A. nancymaae infections; Marisa St. Claire, Max Shapiro, Charlene Shaver, and Rick Fairhurst for assistance producing the cross; Allan Saul for RAP-1 monoclonal antibodies; the Malaria Research and Reference Reagent Resource Center for anti-EBA-175 (deposited by John Adams) and various parasites; Juliana Sá for 7G8 cDNA; David Garboczi and Hua-Poo Su for codon-adjusted RH5; Julian Rayner and John Barnwell for the full-length P. reichenowi RH5 sequence; Mrinal Bhattacharyya, Lisa Ranford-Cartwright, Michael Ferdig, Jigar Patel, Janni Papakrivos, Owen Schwartz, and Juraj Kabat for helpful advice; William E. Collins for the Ghana III parasite line; and Akhil Vaidya and Xin-zhuan Su for discussions. This work was supported by the intramural research program of the NIAID, NIH.

ASJC Scopus subject areas

Virology
Parasitology
Microbiology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.chom.2008.06.001

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Hayton, K., Gaur, D., Liu, A., Takahashi, J., Henschen, B., Singh, S., Lambert, L., Furuya, T., Bouttenot, R., Doll, M., Nawaz, F., Mu, J., Jiang, L., Miller, L. H., & Wellems, T. E. (2008). Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion. Cell Host and Microbe, 4(1), 40-51. https://doi.org/10.1016/j.chom.2008.06.001

@article{f8854934fdf84730ae0ef103dbf80475,

title = "Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion",

abstract = "Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors.",

author = "Karen Hayton and Deepak Gaur and Anna Liu and Jonathan Takahashi and Bruce Henschen and Subhash Singh and Lynn Lambert and Tetsuya Furuya and Rachel Bouttenot and Michelle Doll and Fatima Nawaz and Jianbing Mu and Lubin Jiang and Miller, {Louis H.} and Wellems, {Thomas E.}",

note = "Funding Information: We thank Andre Laughinghouse, Kevin Lee, Robert Gwadz, Brian Keegan, Josh Reece, Cheryl Kothe, Mark Szarowicz, Angela Lunger, Kelly Magee, and Carole Long for help with mosquito and A. nancymaae infections; Marisa St. Claire, Max Shapiro, Charlene Shaver, and Rick Fairhurst for assistance producing the cross; Allan Saul for RAP-1 monoclonal antibodies; the Malaria Research and Reference Reagent Resource Center for anti-EBA-175 (deposited by John Adams) and various parasites; Juliana S{\'a} for 7G8 cDNA; David Garboczi and Hua-Poo Su for codon-adjusted RH5; Julian Rayner and John Barnwell for the full-length P. reichenowi RH5 sequence; Mrinal Bhattacharyya, Lisa Ranford-Cartwright, Michael Ferdig, Jigar Patel, Janni Papakrivos, Owen Schwartz, and Juraj Kabat for helpful advice; William E. Collins for the Ghana III parasite line; and Akhil Vaidya and Xin-zhuan Su for discussions. This work was supported by the intramural research program of the NIAID, NIH. ",

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doi = "10.1016/j.chom.2008.06.001",

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Hayton, K, Gaur, D, Liu, A, Takahashi, J, Henschen, B, Singh, S, Lambert, L, Furuya, T, Bouttenot, R, Doll, M, Nawaz, F, Mu, J, Jiang, L, Miller, LH & Wellems, TE 2008, 'Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion', Cell Host and Microbe, vol. 4, no. 1, pp. 40-51. https://doi.org/10.1016/j.chom.2008.06.001

TY - JOUR

T1 - Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion

AU - Hayton, Karen

AU - Gaur, Deepak

AU - Liu, Anna

AU - Takahashi, Jonathan

AU - Henschen, Bruce

AU - Singh, Subhash

AU - Lambert, Lynn

AU - Furuya, Tetsuya

AU - Bouttenot, Rachel

AU - Doll, Michelle

AU - Nawaz, Fatima

AU - Mu, Jianbing

AU - Jiang, Lubin

AU - Miller, Louis H.

AU - Wellems, Thomas E.

N1 - Funding Information: We thank Andre Laughinghouse, Kevin Lee, Robert Gwadz, Brian Keegan, Josh Reece, Cheryl Kothe, Mark Szarowicz, Angela Lunger, Kelly Magee, and Carole Long for help with mosquito and A. nancymaae infections; Marisa St. Claire, Max Shapiro, Charlene Shaver, and Rick Fairhurst for assistance producing the cross; Allan Saul for RAP-1 monoclonal antibodies; the Malaria Research and Reference Reagent Resource Center for anti-EBA-175 (deposited by John Adams) and various parasites; Juliana Sá for 7G8 cDNA; David Garboczi and Hua-Poo Su for codon-adjusted RH5; Julian Rayner and John Barnwell for the full-length P. reichenowi RH5 sequence; Mrinal Bhattacharyya, Lisa Ranford-Cartwright, Michael Ferdig, Jigar Patel, Janni Papakrivos, Owen Schwartz, and Juraj Kabat for helpful advice; William E. Collins for the Ghana III parasite line; and Akhil Vaidya and Xin-zhuan Su for discussions. This work was supported by the intramural research program of the NIAID, NIH.

PY - 2008/7/17

Y1 - 2008/7/17

N2 - Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors.

AB - Some human malaria Plasmodium falciparum parasites, but not others, also cause disease in Aotus monkeys. To identify the basis for this variation, we crossed two clones that differ in Aotus nancymaae virulence and mapped inherited traits of infectivity to erythrocyte invasion by linkage analysis. A major pathway of invasion was linked to polymorphisms in a putative erythrocyte binding protein, PfRH5, found in the apical region of merozoites. Polymorphisms of PfRH5 from the A. nancymaae-virulent parent transformed the nonvirulent parent to a virulent parasite. Conversely, replacements that removed these polymorphisms from PfRH5 converted a virulent progeny clone to a nonvirulent parasite. Further, a proteolytic fragment of PfRH5 from the infective parasites bound to A. nancymaae erythrocytes. Our results also suggest that PfRH5 is a parasite ligand for human infection, and that amino acid substitutions can cause its binding domain to recognize different human erythrocyte surface receptors.

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JF - Cell Host and Microbe

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ER -

Erythrocyte Binding Protein PfRH5 Polymorphisms Determine Species-Specific Pathways of Plasmodium falciparum Invasion

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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