Dataset Information

Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status.

ABSTRACT: Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterized a novel parasite ligand, Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA), that bound human erythrocytes regardless of Duffy antigen status. PvGAMA was localized at the microneme in the mature schizont-stage parasites. The antibodies against PvGAMA fragments inhibited PvGAMA binding to erythrocytes in a dose-dependent manner. The erythrocyte-specific binding activities of PvGAMA were significantly reduced by chymotrypsin treatment. Thus, PvGAMA may be an adhesion molecule for the invasion of Duffy-positive and -negative human erythrocytes.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC5069673 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status.

Cheng Yang Y Lu Feng F Wang Bo B Li Jian J Han Jin-Hee JH Ito Daisuke D Kong Deok-Hoon DH Jiang Lubin L Wu Jian J Ha Kwon-Soo KS Takashima Eizo E Sattabongkot Jetsumon J Cao Jun J Nyunt Myat Htut MH Kyaw Myat Phone MP Desai Sanjay A SA Miller Louis H LH Tsuboi Takafumi T Han Eun-Taek ET

Scientific reports 20161019

Plasmodium vivax, a major agent of malaria in both temperate and tropical climates, has been thought to be unable to infect humans lacking the Duffy (Fy) blood group antigen because this receptor is critical for erythrocyte invasion. Recent surveys in various endemic regions, however, have reported P. vivax infections in Duffy-negative individuals, suggesting that the parasite may utilize alternative receptor-ligand pairs to complete the erythrocyte invasion. Here, we identified and characterize ...[more]

PMID: 27759110

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Project description:BackgroundThe development of an effective malarial vaccine is an urgent need. Most glycosylphosphatidylinositol (GPI)-anchored proteins of Plasmodium parasites are exposed to neutralizing antibodies, and several are advanced vaccine candidates. In the present study, Plasmodium vivax Pv32 (PVX_084815) as a hypothetical, predicted GPI-anchored and cysteine-rich motif was identified from our previous findings with a focus on its antigenic profiling. The orthologue gene pv32, a predicted GPI anchor of P. falciparum PF3D7_1434400, has still not been well studied.MethodsThe gene information of pv32 was obtained from PlasmoDB. Recombinant Pv32 protein was expressed and purified using a wheat germ cell-free expression system and a glutathione-Sepharose column. Naturally acquired immune response to recombinant Pv32 protein was evaluated using a protein microarray with 96 parasite-infected patients and 96 healthy individuals. Antibodies against recombinant Pv32 proteins from immune animals were produced, used and analyzed for the subcellular localization of native Pv32 protein by an immunofluorescence assay. A total of 48 pv32 sequences from 11 countries retrieved from PlasmoDB were used to determine the genetic diversity, polymorphisms and genealogical relationships with DNAsp and NETWORK software packages.ResultsPv32 is encoded by a conserved gene with two introns that are located on chromosome 13 and expressed as a 32 kDa protein in mature asexual stage parasites. Immunofluorescence data showed that Pv32 localized on the merozoite surface in schizont-stage parasites. The recombinant Pv32 was recognized by 39.6% of antibodies from P. vivax-infected individuals compared with healthy individuals. Low levels of nucleotide diversity (π = 0.0028) and polymorphisms of pv32 were detected within worldwide isolates.ConclusionsThis study shows the identification and characterization of the hypothetical protein, Pv32. Pv32 provides important characteristics, including a merozoite surface protein, a predicted GPI motif and Cysteine-rich motif among Plasmodium species. These results suggested that Pv32 is immunogenic with a merozoite surface pattern to antibodies during natural infection in humans.

Project description:Novel strategies to directly thwart malaria transmission are needed to maintain the gains achieved by current control measures. Transmission-blocking interventions (TBIs), namely vaccines and drugs targeting parasite or mosquito molecules required for vector-stage parasite development, have been recognized as promising approaches for preventing malaria transmission. However, the number of TBI targets is limited and their degree of conservation among the major vector-parasite systems causing human disease is unclear. Therefore, discovery and characterization of novel proteins involved in vector-stage parasite development of Plasmodium falciparum and Plasmodium vivax is paramount. We mined the recent Anopheles gambiae midgut lipid raft proteome for putative mosquito-derived TBI targets and characterized a secreted glycoconjugate of unknown function, AgSGU. We analyzed molecular variation in this protein among a range of anopheline mosquitoes, determined its transcriptomic and proteomic profiles, and conducted both standard and direct membrane feeding assays with P. falciparum (lab/field) and P. vivax (field) in An. gambiae and Anopheles dirus. We observed that α-AgSGU antibodies significantly reduced midgut infection intensity for both lab and field isolates of P. falciparum in An. gambiae and An. dirus. However, no transmission-reducing effects were noted when comparable concentrations of antibodies were included in P. vivax-infected blood meals. Although antibodies against AgSGU exhibit transmission-reducing activity, the high antibody titer required for achieving 80% reduction in oocyst intensity precludes its consideration as a malaria mosquito-based TBI candidate. However, our results suggest that P. falciparum and P. vivax ookinetes use a different repertoire of midgut surface glycoproteins for invasion and that α-AgSGU antibodies, as well as antibodies to other mosquito-midgut microvillar surface proteins, may prove useful as tools for interrogating Plasmodium-mosquito interactions.

Project description:BackgroundPlasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite's ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP) in merozoites and the Duffy antigen receptor for chemokines (DARC) on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown.Methodology/principal findingsUsing whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India.Conclusions/significancePvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests will be required to confirm this hypothesis.

Dataset Information

Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status.

Publications

Plasmodium vivax GPI-anchored micronemal antigen (PvGAMA) binds human erythrocytes independent of Duffy antigen status.

Similar Datasets

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