Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.

The circumsporozoite protein (CSP) plays a key role in malaria sporozoite infection of both mosquito salivary glands and the vertebrate host. The conserved Regions I and II have been well studied but little is known about the immunogenic central repeat region and the N-terminal region of the protein...

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Autores principales: Cassandra Aldrich, Alessandro Magini, Carla Emiliani, Tania Dottorini, Francesco Bistoni, Andrea Crisanti, Roberta Spaccapelo
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:f28459ba4a32425e9455450a53a4359b2021-11-18T07:26:24ZRoles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.1932-620310.1371/journal.pone.0032524https://doaj.org/article/f28459ba4a32425e9455450a53a4359b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22393411/?tool=EBIhttps://doaj.org/toc/1932-6203The circumsporozoite protein (CSP) plays a key role in malaria sporozoite infection of both mosquito salivary glands and the vertebrate host. The conserved Regions I and II have been well studied but little is known about the immunogenic central repeat region and the N-terminal region of the protein. Rodent malaria Plasmodium berghei parasites, in which the endogenous CS gene has been replaced with the avian Plasmodium gallinaceum CS (PgCS) sequence, develop normally in the A. stephensi mosquito midgut but the sporozoites are not infectious. We therefore generated P. berghei transgenic parasites carrying the PgCS gene, in which the repeat region was replaced with the homologous region of P. berghei CS (PbCS). A further line, in which both the N-terminal region and repeat region were replaced with the homologous regions of PbCS, was also generated. Introduction of the PbCS repeat region alone, into the PgCS gene, did not rescue sporozoite species-specific infectivity. However, the introduction of both the PbCS repeat region and the N-terminal region into the PgCS gene completely rescued infectivity, in both the mosquito vector and the mammalian host. Immunofluorescence experiments and western blot analysis revealed correct localization and proteolytic processing of CSP in the chimeric parasites. The results demonstrate, in vivo, that the repeat region of P. berghei CSP, alone, is unable to mediate sporozoite infectivity in either the mosquito or the mammalian host, but suggest an important role for the N-terminal region in sporozoite host cell invasion.Cassandra AldrichAlessandro MaginiCarla EmilianiTania DottoriniFrancesco BistoniAndrea CrisantiRoberta SpaccapeloPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 2, p e32524 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cassandra Aldrich
Alessandro Magini
Carla Emiliani
Tania Dottorini
Francesco Bistoni
Andrea Crisanti
Roberta Spaccapelo
Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
description The circumsporozoite protein (CSP) plays a key role in malaria sporozoite infection of both mosquito salivary glands and the vertebrate host. The conserved Regions I and II have been well studied but little is known about the immunogenic central repeat region and the N-terminal region of the protein. Rodent malaria Plasmodium berghei parasites, in which the endogenous CS gene has been replaced with the avian Plasmodium gallinaceum CS (PgCS) sequence, develop normally in the A. stephensi mosquito midgut but the sporozoites are not infectious. We therefore generated P. berghei transgenic parasites carrying the PgCS gene, in which the repeat region was replaced with the homologous region of P. berghei CS (PbCS). A further line, in which both the N-terminal region and repeat region were replaced with the homologous regions of PbCS, was also generated. Introduction of the PbCS repeat region alone, into the PgCS gene, did not rescue sporozoite species-specific infectivity. However, the introduction of both the PbCS repeat region and the N-terminal region into the PgCS gene completely rescued infectivity, in both the mosquito vector and the mammalian host. Immunofluorescence experiments and western blot analysis revealed correct localization and proteolytic processing of CSP in the chimeric parasites. The results demonstrate, in vivo, that the repeat region of P. berghei CSP, alone, is unable to mediate sporozoite infectivity in either the mosquito or the mammalian host, but suggest an important role for the N-terminal region in sporozoite host cell invasion.
format article
author Cassandra Aldrich
Alessandro Magini
Carla Emiliani
Tania Dottorini
Francesco Bistoni
Andrea Crisanti
Roberta Spaccapelo
author_facet Cassandra Aldrich
Alessandro Magini
Carla Emiliani
Tania Dottorini
Francesco Bistoni
Andrea Crisanti
Roberta Spaccapelo
author_sort Cassandra Aldrich
title Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
title_short Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
title_full Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
title_fullStr Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
title_full_unstemmed Roles of the amino terminal region and repeat region of the Plasmodium berghei circumsporozoite protein in parasite infectivity.
title_sort roles of the amino terminal region and repeat region of the plasmodium berghei circumsporozoite protein in parasite infectivity.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/f28459ba4a32425e9455450a53a4359b
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