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• W2113206880 endingPage "3768" @default.
• W2113206880 startingPage "3758" @default.
• W2113206880 abstract "ABSTRACT Malaria infection starts when sporozoites are transmitted to the mammalian host during a mosquito bite. Sporozoites enter the blood circulation, reach the liver, and infect hepatocytes. The formation of a parasitophorous vacuole (PV) establishes their intracellular niche. Recently, two members of the 6-Cys domain protein family, P52 and P36, were each shown to play an important albeit nonessential role in Plasmodium berghei sporozoite infectivity for the rodent host. Here, we generated p52/p36 -deficient Plasmodium yoelii parasites by the simultaneous deletion of both genes using a single genetic manipulation. p52/p36 -deficient parasites exhibited normal progression through the life cycle during blood-stage infection, transmission to mosquitoes, mosquito-stage development, and sporozoite infection of the salivary glands. p52/p36 -deficient sporozoites also showed normal motility and cell traversal activity. However, immunofluorescence analysis and electron microscopic observations revealed that p52/p36 -deficient parasites did not form a PV within hepatocytes in vitro and in vivo. The p52/p36 -deficient parasites localized as free entities in the host cell cytoplasm or the host cell nucleoplasm and did not develop as liver stages. Consequently, they did not cause blood-stage infections even at high sporozoite inoculation doses. Mice immunized with p52/p36 -deficient sporozoites were completely protected against infectious sporozoite challenge. Our results demonstrate for the first time the generation of two-locus gene deletion-attenuated parasites that infect the liver but do not progress to blood-stage infection. The study will critically guide the design of Plasmodium falciparum live attenuated malaria vaccines." @default.
• W2113206880 created "2016-06-24" @default.
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• W2113206880 date "2007-08-01" @default.
• W2113206880 modified "2023-10-18" @default.
• W2113206880 title "<i>Plasmodium yoelii</i> Sporozoites with Simultaneous Deletion of P52 and P36 Are Completely Attenuated and Confer Sterile Immunity against Infection" @default.
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• W2113206880 doi "https://doi.org/10.1128/iai.00225-07" @default.
• W2113206880 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1951999" @default.
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• W2113206880 hasPublicationYear "2007" @default.
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