Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.

The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of...

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Autores principales:	Mathias Diehl, Lena Roling, Lukas Rohland, Sebastian Weber, Marek Cyrklaff, Cecilia P Sanchez, Carlo A Beretta, Caroline S Simon, Julien Guizetti, Julia Hahn, Norma Schulz, Matthias P Mayer, Jude M Przyborski
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ad3aa796df9c4134ab9f7afc1411acec
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spelling	oai:doaj.org-article:ad3aa796df9c4134ab9f7afc1411acec2021-12-02T20:00:04ZCo-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.1553-73661553-737410.1371/journal.ppat.1009969https://doaj.org/article/ad3aa796df9c4134ab9f7afc1411acec2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009969https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown. Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family. Although parasites lacking this protein were still able to grow in cell culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP. Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that PFA66 functions in concert with a HSP70 to carry out host cell modification. Strikingly, this HSP70 is likely to be of host origin. ATPase assays on recombinant protein verify a functional interaction between PFA66 and residual host cell HSP70. Taken together, our data reveal a role for PFA66 in host cell modification, strongly implicate human HSP70s as being essential in this process and uncover a new KAHRP-independent molecular factor required for correct knob biogenesis.Mathias DiehlLena RolingLukas RohlandSebastian WeberMarek CyrklaffCecilia P SanchezCarlo A BerettaCaroline S SimonJulien GuizettiJulia HahnNorma SchulzMatthias P MayerJude M PrzyborskiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 10, p e1009969 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Mathias Diehl Lena Roling Lukas Rohland Sebastian Weber Marek Cyrklaff Cecilia P Sanchez Carlo A Beretta Caroline S Simon Julien Guizetti Julia Hahn Norma Schulz Matthias P Mayer Jude M Przyborski Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
description	The pathology associated with malaria infection is largely due to the ability of infected human RBCs to adhere to a number of receptors on endothelial cells within tissues and organs. This phenomenon is driven by the export of parasite-encoded proteins to the host cell, the exact function of many of which is still unknown. Here we inactivate the function of one of these exported proteins, PFA66, a member of the J-domain protein family. Although parasites lacking this protein were still able to grow in cell culture, we observed severe defects in normal host cell modification, including aberrant morphology of surface knobs, disrupted presentation of the cytoadherence molecule PfEMP1, and a total lack of cytoadherence, despite the presence of the knob associated protein KAHRP. Complementation assays demonstrate that an intact J-domain is required for recovery to a wild-type phenotype and suggest that PFA66 functions in concert with a HSP70 to carry out host cell modification. Strikingly, this HSP70 is likely to be of host origin. ATPase assays on recombinant protein verify a functional interaction between PFA66 and residual host cell HSP70. Taken together, our data reveal a role for PFA66 in host cell modification, strongly implicate human HSP70s as being essential in this process and uncover a new KAHRP-independent molecular factor required for correct knob biogenesis.
format	article
author	Mathias Diehl Lena Roling Lukas Rohland Sebastian Weber Marek Cyrklaff Cecilia P Sanchez Carlo A Beretta Caroline S Simon Julien Guizetti Julia Hahn Norma Schulz Matthias P Mayer Jude M Przyborski
author_facet	Mathias Diehl Lena Roling Lukas Rohland Sebastian Weber Marek Cyrklaff Cecilia P Sanchez Carlo A Beretta Caroline S Simon Julien Guizetti Julia Hahn Norma Schulz Matthias P Mayer Jude M Przyborski
author_sort	Mathias Diehl
title	Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
title_short	Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
title_full	Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
title_fullStr	Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
title_full_unstemmed	Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
title_sort	co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/ad3aa796df9c4134ab9f7afc1411acec
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Co-chaperone involvement in knob biogenesis implicates host-derived chaperones in malaria virulence.

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