Sequential Processing of Merozoite Surface Proteins during and after Erythrocyte Invasion by Plasmodium falciparum

Boyle, Michelle J.; Langer, Christine; Chan, Jo‐Anne; Hodder, Anthony N.; Coppel, Ross L.; Anders, Robin F.; Beeson, James G.

doi:10.1128/iai.00866-13

Cited by 62 publications

(65 citation statements)

References 83 publications

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“…MSP4 is a 40 kDa GPI-anchored membrane protein expressed on the merozoite surface that appears to be essential because it is refractory to genetic deletion (77,78). Unlike most other known merozoite proteins, MSP4 is taken into the invaded erythrocyte without proteolytic processing and is detectable for several hours postinvasion (79). In a recent cross-sectional study in malaria-exposed individuals in the Brazilian Amazon (80), plasma from asymptomatic individuals reacted more strongly to recombinant MSP4 protein than those from symptomatic cases, but anti-MSP4 antibodies could not be independently associated with asymptomatic status.…”

Section: S)mentioning

confidence: 99%

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Finney

Danziger

Molina

et al. 2014

Molecular & Cellular Proteomics

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Malaria remains one of the most prevalent and lethal human infectious diseases worldwide. A comprehensive characterization of antibody responses to blood stage malaria is essential to support the development of future vaccines, sero-diagnostic tests, and sero-surveillance methods. We constructed a proteome array containing 4441 recombinant proteins expressed by the blood stages of the two most common human malaria parasites, P. falciparum (Pf) and P. vivax (Pv), and used this array to screen sera of Papua New Guinea children infected with Pf, Pv, or both (Pf/Pv) that were either symptomatic (febrile), or asymptomatic but had parasitemia detectable via microscopy or PCR. We hypothesized that asymptomatic children would develop antigen-specific antibody profiles associated with antidisease immunity, as compared with symptomatic children. The sera from these children recognized hundreds of the arrayed recombinant Pf and Pv proteins. In general, responses in asymptomatic children were highest in those with high parasitemia, suggesting that antibody levels are associated with parasite burden. In contrast, symptomatic children carried fewer antibodies than asymptomatic children with infections detectable by microscopy, particularly in Pv and Pf/Pv groups, suggesting that antibody production may be impaired during symptomatic infections. We used machine-learning algorithms to investigate the relationship between antibody responses and symptoms, and we identified antibody responses to sets of Plasmodium proteins that could predict clinical status of the donors. Several of these antibody responses were identified by multiple comparisons, including those against members of the serine enriched repeat antigen family and merozoite protein 4. Interestingly, both P. falciparum serine enriched repeat antigen-5 and merozoite protein 4 have been previously investigated for use in vaccines. This machine learning approach, never previously applied to proteome arrays, can be used to generate a list of potential seroprotective and/or diagnostic antigens candidates that can be further evaluated in longitudinal studies. Molecular & Cellular

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Section: S)mentioning

confidence: 99%

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Finney

Danziger

Molina

et al. 2014

Molecular & Cellular Proteomics

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“…Out of the multigene families found in all known primate and rodent malarias, two ( msp3 and msp7 ) are expressed on the surface of asexual stage (merozoite) parasites and are considered part of a group commonly known as the Merozoite Surface Proteins (MSPs). These MSPs, together with other proteins, are involved in the invasion of host red-blood cells (Boyle et al, 2014). …”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the msp3 genes in P. vivax ( Pvmsp3 ) and their orthologs from related species parasitizing non-human primates in Southeast Asia, are not orthologs to those identified as the Pfmsp3 family in P. falciparum and its related species (Rice et al, 2014). This leaves msp7 as the only MSP gene family, with a role in erythrocyte invasion, found across all the known primate and rodent malarial parasites (Boyle et al, 2014). Although this pattern suggests its importance, there is still limited functional information on msp7.…”

Section: Introductionmentioning

confidence: 99%

Evolution of the merozoite surface protein 7 ( msp7 ) family in Plasmodium vivax and P . falciparum : A comparative approach

Castillo

Pacheco

Escalante

2017

Infection, Genetics and Evolution

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Malaria parasites (genus Plasmodium) are a diverse group found in many species of vertebrate hosts. These parasites invade red blood cells in a complex process comprising several proteins, many encoded by multigene families, one of which is merozoite surface protein-7 (msp7). In the case of Plasmodium vivax, the most geographically widespread human-infecting species, differences in the number of paralogs within multigene families have been previously explained, at least in part, as potential adaptations to the human host. To investigate this in msp7, we studied its orthologs in closely related nonhuman primate parasites; investigating both paralog evolutionary history and genetic polymorphism. The emerging patterns were then compared with the human parasite Plasmodium falciparum. We found that the evolution of the msp7 family is consistent with a birth-and-death model, where duplications, pseudogenizations, and gene loss events are common. However, all paralogs in P. vivax and P. falciparum had orthologs in their closely related species in non-human primates indicating that the ancestors of those paralogs precede the events leading to their origins as human parasites. Thus, the number of paralogs cannot be explained as an adaptation to human hosts. Although there is no functional information for msp7 in P. vivax, we found evidence for purifying selection in the genetic polymorphism of some of its paralogs as well as their orthologs in closely related non-human primate parasites. We also found evidence indicating that a few of P. vivax’s paralogs may have diverged from their orthologs in non-human primates by episodic positive selection. Hence, they may had been under selection when the lineage leading to P. vivax diverged from the Asian non-human primates and switched into Homininae. All these lines of evidence suggest that msp7 is functionally important in P. vivax.

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“…The glycosylphosphatidylinositol (GPI)-anchored stub of MSP1, MSP1 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] , is known to be retained by the parasite for several hours after invasion and may play a role in the formation of the food vacuole (30,31). A role for the stub of AMA1 in T. gondii has been similarly hypothesized (32).…”

Section: Please Remove Your Coat At the Doormentioning

confidence: 99%

Inside Scoop on Outside Proteins

Dvorin

2014

Infect Immun

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Invasion into red blood cells is an essential step in the life cycle of parasites that cause human malaria. Antibodies targeting the key parasite proteins in this process are important for developing a protective immune response. In the current issue, Boyle and colleagues provide a detailed examination of Plasmodium falciparum invasion and specifically illuminate the fate of surfaceexposed parasite proteins during and immediately after invasion.H uman malaria remains a leading cause of death and disease worldwide. Recent estimates suggest that there were 225 million cases of malaria in 2009, with more than 1 million deaths in 2010 (1, 2). The parasite Plasmodium falciparum causes the most severe forms of malaria. Resistance to existing antimalarial medications is a constant and continually emerging hurdle to the effective treatment of malaria. At the same time, efforts to find a broadly effective vaccine providing sustained protection have not yet been successful. For these reasons, and many more, a more intricate understanding of the molecular details of the parasite life cycle is needed. Knowledge of the molecular mechanism of parasite invasion, replication, and egress will hopefully provide new targets for antimalarial therapeutics and vaccines. The work described in this issue by Boyle and colleagues (3) provides a new layer of complexity in our understanding of P. falciparum invasion into human red blood cells (RBCs). PLASMODIUM FALCIPARUM: AN EVASIVE INVADERAfter a susceptible person is bitten by an infected female Anopheles mosquito, P. falciparum sporozoites travel to the liver and invade hepatic cells. Inside the hepatocyte, the sporozoite differentiates and produces thousands of RBC-invasive merozoites (4). Once released from the protected intracellular environment, a merozoite has a very limited window of time to find and invade a RBC or risks clearance by the host reticuloendothelial system and/or inactivation by antibodies. Several elegant studies have described the basic steps of merozoite invasion of (Fig. 1). The predominant model of parasite invasion proposes that the merozoite reversibly binds the surface of the RBC via multiple lowaffinity interactions between parasite-expressed merozoite surface proteins (MSPs) and RBC surface proteins (e.g., Band 3) or heparin-like glycosaminoglycans (13-15). The invading merozoite must reorient itself to bring the apical end, with its associated apical organelles (rhoptries, micronemes, and dense granules), into direct contact with the RBC surface. Reorientation likely requires the action of P. falciparum apical membrane protein 1 (PfAMA1) (7). Interestingly, the "receptor" for PfAMA1 is another parasite protein, RON2, that is injected into the host side of the RBC membrane (16,17). Following reorientation, the merozoite forms an irreversible attachment to the RBC, known as the tight junction, which is made in part from the PfAMA1-RON2 interaction. The formation of the tight junction likely involves multiple interactions between parasite ligands located i...

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Sequential Processing of Merozoite Surface Proteins during and after Erythrocyte Invasion by Plasmodium falciparum

Cited by 62 publications

References 83 publications

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Predicting Antidisease Immunity Using Proteome Arrays and Sera from Children Naturally Exposed to Malaria

Evolution of the merozoite surface protein 7 ( msp7 ) family in Plasmodium vivax and P . falciparum : A comparative approach

Inside Scoop on Outside Proteins

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