Plasmodium vivax Merozoite Surface Protein-3 (PvMSP3): Expression of an 11 Member Multigene Family in Blood-Stage Parasites

• Type of Material: Article
• Authors: Jianlin Jiang, Emory University; John W. Barnwell, Centers for Disease Control and Prevention; Esmeralda V S Meyer, Emory University; Mary R Galinski, Emory University
• Language: English
• Date: 2013-05-23
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063888
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 8
• Issue: 5
• Start Page: e63888
• End Page: e63888
• Grant/Funding Information: The Yerkes National Primate Research Center received support from the National Center for Research Resources P51RR000165, and it is currently supported by the Office of Research Infrastructure Programs/OD P51OD011132.; This research was funded by the National Institutes of Health, National Institute for Allergy and Infectious Diseases to MRG (1R01AI24710 and R21AI094449).
• Research Categories: Health Sciences, Public Health

Abstract

Background Three members of the Plasmodium vivax merozoite surface protein-3 (PvMSP3) family (PvMSP3-α, PvMSP3-β and PvMSP3-γ) were initially characterized and later shown to be part of a larger highly diverse family, encoded by a cluster of genes arranged head-to-tail in chromosome 10. PvMSP3-α and PvMSP3-β have become genetic markers in epidemiological studies, and are being evaluated as vaccine candidates. This research investigates the gene and protein expression of the entire family and pertinent implications. Methodology/Principal Findings A 60 kb multigene locus from chromosome 10 in P. vivax (Salvador 1 strain) was studied to classify the number of pvmsp3 genes present, and compare their transcription, translation and protein localization patterns during blood-stage development. Eleven pvmsp3 paralogs encode an N-terminal NLRNG signature motif, a central domain containing repeated variable heptad sequences, and conserved hydrophilic C-terminal features. One additional ORF in the locus lacks these features and was excluded as a member of the family. Transcripts representing all eleven pvmsp3 genes were detected in trophozoite- and schizont-stage RNA. Quantitative immunoblots using schizont-stage extracts and antibodies specific for each PvMSP3 protein demonstrated that all but PvMSP3.11 could be detected. Homologs were also detected by immunoblot in the closely related simian species, P. cynomolgi and P. knowlesi. Immunofluorescence assays confirmed that eight of the PvMSP3s are present in mature schizonts. Uniquely, PvMSP3.7 was expressed exclusively at the apical end of merozoites. Conclusion/Significance Specific proteins were detected representing the expression of 10 out of 11 genes confirmed as members of the pvmsp3 family. Eight PvMSP3s were visualized surrounding merozoites. In contrast, PvMSP3.7 was detected at the apical end of the merozoites. Pvmsp3.11 transcripts were present, though no corresponding protein was detected. PvMSP3 functions remain unknown. The ten expressed PvMSP3s are predicted to have unique and complementary functions in merozoite biology.