Gametocyte-Forming and Non-Gametocyte-Forming Clones of Plasmodium Falciparum

Bhasin, Veena; Trager, William

doi:10.4269/ajtmh.1984.33.534

Cited by 123 publications

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“…falciparum Parasites. P. falciparum clones used in this study were Dd2 (7), Dd2/NM1 (7), 3D7 (24), and HB3 (25). The parasites were grown as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion

Gaur

Singh²,

Singh³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

133

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Plasmodium falciparum invasion of human erythrocytes involves several parasite and erythrocyte receptors that enable parasite invasion by multiple redundant pathways. A key challenge to the development of effective vaccines that block parasite infection of erythrocytes is identifying the players in these pathways and determining their function. Invasion by the parasite clone, Dd2, requires sialic acid on the erythrocyte surface; Dd2/NM is a variant selected for its ability to invade neuraminidase-treated erythrocytes that lack sialic acid. The P. falciparum protein, reticulocyte homology 4 (PfRH4), is uniquely up-regulated in Dd2/NM compared with Dd2, suggesting that it may be a parasite receptor involved in invasion. The aim of the present study was to determine the role of PfRH4 in invasion of erythrocytes and to determine whether it is a target of antibody-mediated blockade and thus a vaccine candidate. We show that both native PfRH4 and a recombinant 30-kDa protein to a conserved region of PfRH4 (rRH430) bind strongly to neuraminidase-treated erythrocytes. rRH430 blocks both the erythrocyte binding of the native PfRH4 and invasion of neuraminidase-treated erythrocytes by Dd2/NM. Taken together, these results indicate that PfRH4 is a parasite receptor involved in sialic acid-independent invasion of erythrocytes. Although antibodies to rRH430 block binding of the native protein to erythrocytes, these antibodies failed to block invasion. These findings suggest that, although PfRH4 is required for invasion of neuraminidase-treated erythrocytes by Dd2/NM, it is inaccessible for antibody-mediated inhibition of the invasion process.erythrocyte invasion ͉ red cell invasion ͉ invasion pathways ͉ erythrocyte binding ͉ sialic acids U nlike Plasmodium vivax, which depends completely on the single interaction of the parasite's Duffy binding protein with the Duffy blood group antigen on erythrocytes (1, 2), Plasmodium falciparum exploits multiple parasite receptors to invade erythrocytes. The redundancy in molecular interactions allows P. falciparum to use alternate pathways for invasion of human erythrocytes. The full repertoire of parasite receptors is not yet identified, and the role in alternate invasion pathways of those identified still remains to be fully defined (3-5).Most of the parasite receptors that are known to play a role in erythrocyte binding and invasion of Plasmodium can be classified into two families. First, the Duffy binding-like (DBL) family that includes the P. vivax/Plasmodium knowlesi Duffy binding proteins and the P. falciparum erythrocyte binding-like proteins (EBA-175, BAEBL, JESEBL, EBL-1, and PEBL). Second, the reticulocyte binding-like (RBL) family that includes the Plasmodium yoelii 235-kDa rhoptry proteins, the P. vivax reticulocyte binding proteins (PvRBP-1 and -2), and the P. falciparum reticulocyte homology (PfRH) proteins (PfRH1, PfRH2a, PfRH2b, PfRH3, PfRH4, and PfRH5) (3-5).Here, we focus on one member of the PfRH family of parasite receptors, P. falciparum reticulocyte homology 4, P...

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“…falciparum Parasites. P. falciparum clones used in this study were Dd2 (7), Dd2/NM1 (7), 3D7 (24), and HB3 (25). The parasites were grown as described in ref.…”

Section: Methodsmentioning

confidence: 99%

Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion

Gaur

Singh²,

Singh³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

133

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“…The preparation of knob' and knob-uncloned (referred to as wild-type) FCR-3 (7), FCR-3 knob' clone A-2 and knobclone D-4 (17), and FCR-3 knob-clone C-6 and knob' clone C-3 (6) has been described. The knob' clone HB-3 was prepared from a Honduran isolate (18). In vitro cultures were maintained in Petri dishes in a candlejar (19).…”

Section: Methodsmentioning

confidence: 99%

Histidine-rich domain of the knob protein of the human malaria parasite Plasmodium falciparum.

Kilejian¹,

Sharma²,

Karoui³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

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Membranes of erythrocytes infected with the human malaria parasite Plasmodium fakiparum develop protrusions called knobs. These structures are essential for the survival of the parasite in the host, and their induction requires the synthesis of the knob protein by the parasite. We describe the isolation of a cDNA clone encoding the amino-terminal half of the knob protein. A cDNA library was constructed from RNA prepared from ring stages of a P. fakiparum isolate that has retained its ability to induce knobs (knob' phenotype). A synthetic oligonucleotide probe encoding polyhistidine was used to isolate the cDNA clone, which encodes the aminoterminal half of a polypeptide with all the known attributes of the knob protein. The gene is not transcribed in variants that do not synthesize the knob protein and thereby cannot induce knobs (knob-phenotype). The apparent lack of transcription in knob-variants is due to different mechanisms: although the gene is present in one knob-isolate, it has been deleted in a cloned knob-variant. The primary structure of the polypeptide deduced from a partial sequence of the cDNA is distinctly different from other malarial histidine-rich polypeptides. The amino-terminal sequence shows the characteristic features of a signal peptide. This is followed by a histidine-rich domain and a subsequent region which contains one histidine. Peptide map analysis of the knob protein is consistent with the structural features deduced from the sequence analysis of the cDNA.

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“…These four parasite isolates all appear to have origins distinct from those of the FCR3 parasite, whose exact provenance is unknown due to historical contamination but which groups with southeast Asian isolates by DNA genotyping (26). Whereas FCR3, 3D7, HB3, and 7G8 parasites have been cloned in vitro and represent single-parasite genotypes (7,29), the Pl0711 has only recently been adapted to in vitro cultivation and is likely to contain more than one parasite genotype (17).…”

Section: Expression Ofmentioning

confidence: 99%

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

et al. 2008

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Pregnancy-associated malaria (PAM) is characterized by the placental sequestration of Plasmodium falciparum-infected erythrocytes (IEs) with the ability to bind to chondroitin sulfate A (CSA). VAR2CSA is a leading candidate for a pregnancy malaria vaccine, but its large size (ϳ350 kDa) and extensive polymorphism may pose a challenge to vaccine development. In this study, rabbits were immunized with individual VAR2CSA Duffy binding-like (DBL) domains expressed in Pichia pastoris or var2csa plasmid DNA and sera were screened on different CSA-binding parasite lines. Rabbit antibodies to three recombinant proteins (DBL1, DBL3, and DBL6) and four plasmid DNAs (DBL1, DBL3, DBL5, and DBL6) reacted with homologous FCR3-CSA IEs. By comparison, antibodies to the DBL4 domain were unable to react with native VAR2CSA protein unless it was first partially proteolyzed with trypsin or chymotrypsin. To investigate the antigenic relationship of geographically diverse CSA-binding isolates, rabbit immune sera were screened on four heterologous CSA-binding lines from different continental origins. Antibodies did not target conserved epitopes exposed in all VAR2CSA alleles; however, antisera to several DBL domains cross-reacted on parasite isolates that had polymorphic loops in common with the homologous immunogen. This study demonstrates that VAR2CSA contains common polymorphic epitopes that are shared between geographically diverse CSA-binding lines.

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Gametocyte-Forming and Non-Gametocyte-Forming Clones of Plasmodium Falciparum

Cited by 123 publications

References 0 publications

Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion

Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion

Histidine-rich domain of the knob protein of the human malaria parasite Plasmodium falciparum.

Evidence for Globally Shared, Cross-Reacting Polymorphic Epitopes in the Pregnancy-Associated Malaria Vaccine Candidate VAR2CSA

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