Dataset Information

First characterization of Plasmodium vivax liver stage antigen (PvLSA) using synthetic peptides.

ABSTRACT:

Background

Plasmodium vivax is the most widespread human malaria in tropical and subtropical countries, including the Republic of Korea. Vivax malaria is characterized by hypnozoite relapse and long latency infection by the retained liver stage of P. vivax, and somewhat surprisingly, little is known of the liver stage antigens of this parasite. Here, we report for the first time the characterization of a liver stage antigen of P. vivax (PvLSA).

Methods

Five peptides located inside PvLSA were synthesized, and specific anti-sera to the respective peptides were used to localize PvLSA on P. vivax parasites in human liver cells by immunofluorescence. Western blotting and enzyme-linked immunosorbent assay were performed using the five peptides and sera collected from vivax malaria patients and from normal healthy controls.

Results

PvLSA was localized on P. vivax parasites in human liver cells. Vivax malaria-infected patients were detected using the five peptides by western blotting. Furthermore, the peptides reacted with the sera of vivax malaria patients.

Conclusions

These results suggest that PvLSA may function during the liver stage of P. vivax.

SUBMITTER: Goo YK

PROVIDER: S-EPMC3925417 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Publications

First characterization of Plasmodium vivax liver stage antigen (PvLSA) using synthetic peptides.

Goo Youn-Kyoung YK Seo Eun-Jeong EJ Choi Yeon-Kyung YK Shin Hyun-Il HI Sattabongkot Jetsumon J Ji So-Young SY Chong Chom-Kyu CK Cho Shin-Hyung SH Lee Won-Ja WJ Kim Jung-Yeon JY

Parasites & vectors 20140212

<h4>Background</h4>Plasmodium vivax is the most widespread human malaria in tropical and subtropical countries, including the Republic of Korea. Vivax malaria is characterized by hypnozoite relapse and long latency infection by the retained liver stage of P. vivax, and somewhat surprisingly, little is known of the liver stage antigens of this parasite. Here, we report for the first time the characterization of a liver stage antigen of P. vivax (PvLSA).<h4>Methods</h4>Five peptides located inside ...[more]

PMID: 24520895

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Project description:Plasmodium vivax is the causative infectious agent of 80-300 million annual cases of malaria. Many aspects of this parasite's biology remain unknown. To further elucidate the interaction of P. vivax with its Saimiri boliviensis host, we obtained detailed proteomes of infected red blood cells, representing the trophozoite-enriched stage of development. Data from two of three biological replicate proteomes, emphasized here, were analyzed using five search engines, which enhanced identifications and resulted in the most comprehensive P. vivax proteomes to date, with 1375 P. vivax and 3209 S. boliviensis identified proteins. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with P. vivax's known reticulocyte host-cell specificity. A majority of the host and pathogen proteins identified belong to specific functional categories, and several parasite gene families, while 33% of the P. vivax proteins have no reported function. Hemoglobin was significantly oxidized in both proteomes, and additional protein oxidation and nitration was detected in one of the two proteomes. Detailed analyses of these post-translational modifications are presented. The proteins identified here significantly expand the known P. vivax proteome and complexity of available host protein functionality underlying the host-parasite interactive biology, and reveal unsuspected oxidative modifications that may impact protein function.Plasmodium vivax malaria is a serious neglected disease, causing an estimated 80 to 300 million cases annually in 95 countries. Infection can result in significant morbidity and possible death. P. vivax, unlike the much better-studied Plasmodium falciparum species, cannot be grown in long-term culture, has a dormant form in the liver called the hypnozoite stage, has a reticulocyte host-cell preference in the blood, and creates caveolae vesicle complexes at the surface of the infected reticulocyte membranes. Studies of stage-specific P. vivax expressed proteomes have been limited in scope and focused mainly on pathogen proteins, thus limiting understanding of the biology of this pathogen and its host interactions. Here three P. vivax proteomes are reported from biological replicates based on purified trophozoite-infected reticulocytes from different Saimiri boliviensis infections (the main non-human primate experimental model for P. vivax biology and pathogenesis). An in-depth analysis of two of the proteomes using 2D LC/MS/MS and multiple search engines identified 1375 pathogen proteins and 3209 host proteins. Numerous functional categories of both host and pathogen proteins were identified, including several known P. vivax protein family members (e.g., PHIST, eTRAMP and VIR), and 33% of protein identifications were classified as hypothetical. Ribosome subunit proteins were noted for both P. vivax and S. boliviensis, consistent with this parasite species' known reticulocyte host-cell specificity. In two biological replicates analyzed for post-translational modifications, hemoglobin was extensively oxidized, and various other proteins were also oxidized or nitrated in one of the two replicates. The cause of such protein modification remains to be determined but could include oxidized heme and oxygen radicals released from the infected red blood cell's parasite-induced acidic digestive vacuoles. In any case, the data suggests the presence of distinct infection-specific conditions whereby both the pathogen and host infected red blood cell proteins may be subject to significant oxidative stress.

Project description:Plasmodium vivax, one species of parasite causing human malaria, forms a dormant liver stage, termed the hypnozoite, which activate weeks, months or years after the primary infection, causing relapse episodes. Relapses significantly contribute to the vivax malaria burden and are only killed with drugs of the 8-aminoquinoline class, which are contraindicated in many vulnerable populations. Development of new therapies targeting hypnozoites is hindered, in part, by the lack of robust methods to continuously culture and characterize this parasite. As a result, the determinants of relapse periodicity and the molecular processes that drive hypnozoite formation, persistence, and activation are largely unknown. While previous reports have described vastly different liver-stage growth metrics attributable to which hepatocyte donor lot is used to initiate culture, a comprehensive assessment of how different P. vivax patient isolates behave in the same lots at the same time is logistically challenging. Using our primary human hepatocyte-based P. vivax liver-stage culture platform, we aimed to simultaneously test the effects of how hepatocyte donor lot and P. vivax patient isolate influence the fate of sporozoites and growth of liver schizonts. We found that, while environmental factors such as hepatocyte donor lot can modulate hypnozoite formation rate, the P. vivax case is also an important determinant of the proportion of hypnozoites observed in culture. In addition, we found schizont growth to be mostly influenced by hepatocyte donor lot. These results suggest that, while host hepatocytes harbor characteristics making them more- or less-supportive of a quiescent versus growing intracellular parasite, sporozoite fating toward hypnozoites is isolate-specific. Future studies involving these host-parasite interactions, including characterization of individual P. vivax strains, should consider the impact of culture conditions on hypnozoite formation, in order to better understand this important part of the parasite's lifecycle.

Dataset Information

First characterization of Plasmodium vivax liver stage antigen (PvLSA) using synthetic peptides.

Background

Methods

Results

Conclusions

Publications

First characterization of Plasmodium vivax liver stage antigen (PvLSA) using synthetic peptides.

Similar Datasets

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