In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 10 ( 2021-10-6), p. e1009969-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009969
DOI:
10.1371/journal.ppat.1009969.g001
DOI:
10.1371/journal.ppat.1009969.g002
DOI:
10.1371/journal.ppat.1009969.g003
DOI:
10.1371/journal.ppat.1009969.g004
DOI:
10.1371/journal.ppat.1009969.g005
DOI:
10.1371/journal.ppat.1009969.g006
DOI:
10.1371/journal.ppat.1009969.g007
DOI:
10.1371/journal.ppat.1009969.s001
DOI:
10.1371/journal.ppat.1009969.s002
DOI:
10.1371/journal.ppat.1009969.s003
DOI:
10.1371/journal.ppat.1009969.s004
DOI:
10.1371/journal.ppat.1009969.s005
DOI:
10.1371/journal.ppat.1009969.s006
DOI:
10.1371/journal.ppat.1009969.s007
DOI:
10.1371/journal.ppat.1009969.s008
DOI:
10.1371/journal.ppat.1009969.s009
DOI:
10.1371/journal.ppat.1009969.s010
DOI:
10.1371/journal.ppat.1009969.s011
DOI:
10.1371/journal.ppat.1009969.s012
DOI:
10.1371/journal.ppat.1009969.s013
DOI:
10.1371/journal.ppat.1009969.s014
DOI:
10.1371/journal.ppat.1009969.s015
DOI:
10.1371/journal.ppat.1009969.s016
DOI:
10.1371/journal.ppat.1009969.s017
DOI:
10.1371/journal.ppat.1009969.s018
DOI:
10.1371/journal.ppat.1009969.r001
DOI:
10.1371/journal.ppat.1009969.r002
DOI:
10.1371/journal.ppat.1009969.r003
DOI:
10.1371/journal.ppat.1009969.r004
DOI:
10.1371/journal.ppat.1009969.r005
DOI:
10.1371/journal.ppat.1009969.r006
DOI:
10.1371/journal.ppat.1009969.r007
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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