{ "abstract": "The parasitoid wasp Ganaspis hookeri infects Drosophila melanogaster larvae, laying an egg and injecting venom directly into the host body cavity. While infected hosts mount an immune response in an attempt to eliminate the parasitoid egg, parasitoid venom proteins act to inhibit these host responses and manipulate host physiology to ensure infection success. A key immune suppressive venom protein in G. hookeri is a venom-specific isoform of the SERCA (Sarco/endoplasmic reticulum calcium-ATPase) calcium pump. However, SERCA is a large hydrophobic protein, and the mechanism by which it and other venom proteins are transported into host cells is not well understood. Electron microscopy and nanoparticle tracking analysis of G. hookeri venom revealed the presence of venom extracellular vesicles (vEVs) as a putative transport mechanism. We characterized the biophysical properties of vEVs, and found that G. hookeri venom contains multiple vesicle types that are distinguishable by size, zeta potential, protein content, and density. A subset of these vEVs contain SERCA, and we found that fluorescently labeled vEVs are able to enter into host immune cells and alter host intracellular calcium levels, and that disruption of vesicle integrity results in the loss of this SERCA activity in host cells. Together, our data support a model in which G. hookeri venom proteins, including SERCA, are packaged into an array of venom vesicles, and are transported into host cells for immune suppression. Author summary: Upon infection, parasites introduce virulence factors into the host cells in an attempt to overcome the host immune response. While many virulence proteins are easily secreted, large, hydrophobic virulence factors have been identified in many parasites, including in the venoms of parasitoid wasps. We used the Drosophila melanogaster-parasitoid wasp experimental system to identify and characterize the packaging of venom proteins into venom extracellular vesicles in the parasitoid Ganaspis hookeri. We further found that disruption of vesicle integrity inhibits the anti-immune function of venom. The use of extracellular vesicles to transport virulence proteins is widely conserved, including among human-infecting parasites, and our biophysical characterization of venom extracellular vesicles opens the door for understanding this understudied aspect of infection biology.", "abstract_shown": true, "affiliations": [ "Department of Biochemistry & Biophysics, Oregon State University, Corvallis, Oregon, United States of America.", "School of Biological Sciences, Illinois State University, Normal, Illinois, United States of America.", "Electron Microscopy Facility, Oregon State University, Corvallis, Oregon, United States of America.", "Department of Chemistry, Illinois State University, Normal, Illinois, United States of America.", "Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama, United States of America." ], "article_type": "Research Article", "arxiv": null, "author_total": 7, "authors": [ { "affs": [ 0, 1 ], "name": "Nicholas M Bretz" }, { "affs": [ 1 ], "name": "Chris Lark" }, { "affs": [ 0 ], "name": "Sarah Perkel" }, { "affs": [ 2 ], "name": "Rebecca Jackson" }, { "affs": [ 3 ], "name": "Jeremy D Driskell" }, { "affs": [ 4 ], "name": "James A Mobley" }, { "affs": [ 0, 1 ], "name": "Nathan T Mortimer", "orcid": "0000-0003-3787-9445" } ], "bibtex": "https://research.draconitic.com/paper/eh19se3e6bb6h.bib", "cited_by": 0, "doi": "10.1371/journal.ppat.1014707", "fulltext_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014707", "id": "eh19se3e6bb6h", "issns": [ "1553-7374", "1553-7366" ], "landing_url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014707", "language": "eng", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2403|Invertebrate Immune Response Mechanisms" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular structures and organelles/Vesicles" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Blood cells/White blood cells/Hemocytes" ], [ "plos", "/Biology and life sciences/Cell biology/Cellular types/Animal cells/Immune cells/White blood cells/Hemocytes" ], [ "plos", "/Biology and life sciences/Developmental biology/Life cycles/Larvae" ], [ "plos", "/Biology and life sciences/Immunology/Immune cells/White blood cells/Hemocytes" ], [ "plos", "/Biology and life sciences/Microbiology/Virology/Viral transmission and infection/Host cells" ], [ "plos", "/Biology and life sciences/Organisms/Eukaryota/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Biology and life sciences/Toxicology/Toxic agents/Toxins/Venoms" ], [ "plos", "/Biology and life sciences/Zoology/Animals/Invertebrates/Arthropoda/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Biology and life sciences/Zoology/Entomology/Insects/Drosophila/Drosophila melanogaster" ], [ "plos", "/Medicine and health sciences/Immunology/Immune cells/White blood cells/Hemocytes" ], [ "plos", "/Medicine and health sciences/Medical conditions/Parasitic diseases" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Virulence factors" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Toxicology/Toxic agents/Toxins/Venoms" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Animal models/Drosophila melanogaster" ], [ "plos", "/Research and analysis methods/Animal studies/Experimental organism systems/Model organisms/Drosophila melanogaster" ], [ "plos", "/Research and analysis methods/Model organisms/Drosophila melanogaster" ] ], "openalex": "W7222736714", "pdf_url": "https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1014707&type=printable", "pmcid": "PMC13693980", "pmid": "42886768", "published": "2026-10-16", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/eh19se3e6bb6h.ris", "sources": [ { "first_seen": "2026-10-30T12:17:23Z", "native_id": "10.1371/journal.ppat.1014707", "source": "plos", "url": "https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014707" }, { "first_seen": "2026-10-30T12:18:46Z", "native_id": "MED:42886768", "source": "europepmc", "url": "https://europepmc.org/article/MED/42886768" } ], "subjects": [ { "field": "biology", "origin": "plos:cell biology", "subfield": "cell-biology" }, { "field": "biology", "origin": "plos:immunology", "subfield": "immunology" }, { "field": "medicine", "origin": "plos:toxicology", "subfield": "pharmacology-toxicology" } ], "title": "Venom vesicles from the parasitoid Ganaspis hookeri facilitate venom protein entry into host immune cells", "title_text": "Venom vesicles from the parasitoid Ganaspis hookeri facilitate venom protein entry into host immune cells", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:46Z", "url": "https://research.draconitic.com/paper/eh19se3e6bb6h", "venue": "PLOS Pathogens", "versions": [] }