{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:35:31Z","timestamp":1775072131578,"version":"3.50.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021671","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Fund of Khon Kaen University"},{"name":"the National Science, Research and Innovation Fund"},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Opisthorchiasis remains a significant public health concern throughout Southeast Asia. The liver fluke Opisthorchis viverrini resides within the biliary tract, and chronic infection leads to bile duct cancer, or cholangiocarcinoma. Here, we examined the functions of liver fluke tetraspanins, 4\u2013transmembrane domain proteins expressed on the surface of the fluke tegument, and extracellular vesicles (EVs) derived from this syncytial surface. We undertook CRISPR-Cas9 gene knockout (KO) of the O viverrini tetraspanin 2 (Ov-tsp-2) gene and found that Ov-tsp-2-KO flukes had abnormal tegument biogenesis. The tegument of Ov-tsp-2-KO flukes was increasingly vacuolated, and fewer EVs were secreted. EVs that were secreted were deficient in Ov-TSP-2, and their uptake by cholangiocytes was diminished. The findings indicate a critical role for Ov-TSP-2 in maintenance of the tegument, EV production, and uptake by host target cells; they also support the development of this parasite antigen as an anti-infection and anticancer vaccine for opisthorchiasis and opisthorchiasis-associated cholangiocarcinoma.<\/jats:p>","DOI":"10.1093\/infdis\/jiaf466","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T11:42:28Z","timestamp":1756899748000},"page":"e510-e520","source":"Crossref","is-referenced-by-count":1,"title":["Gene Editing of a Carcinogenic Liver Fluke Tetraspanin Impairs Parasite Surface Biogenesis and Extracellular Vesicle Uptake by Human Host Cells"],"prefix":"10.1093","volume":"233","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8536-8589","authenticated-orcid":false,"given":"Sujittra","family":"Chaiyadet","sequence":"first","affiliation":[{"name":"Department of Tropical Medicine, Faculty of Medicine, Khon Kaen University , Khon Kaen ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wannaporn","family":"Ittiprasert","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University , Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6937-0112","authenticated-orcid":false,"given":"Michael J","family":"Smout","sequence":"additional","affiliation":[{"name":"Australian Institute of Tropical Health and Medicine, James Cook University , Cairns , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1585-495X","authenticated-orcid":false,"given":"Ladawan","family":"Khowawisetsut","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine Siriraj Hospital, Mahidol University , Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Apisit","family":"Ruangsuwast","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Khon Kaen University , Khon Kaen ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0002","authenticated-orcid":false,"given":"Paul J","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University , Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0896-8441","authenticated-orcid":false,"given":"Alex","family":"Loukas","sequence":"additional","affiliation":[{"name":"Australian Institute of Tropical Health and Medicine, James Cook University , Cairns , Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thewarach","family":"Laha","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Faculty of Medicine, Khon Kaen University , Khon Kaen ,","place":["Thailand"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"2026031304531774200_jiaf466-B1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.pt.2012.07.006","article-title":"The tumorigenic liver fluke Opisthorchis viverrini\u2014multiple pathways to cancer","volume":"28","author":"Sripa","year":"2012","journal-title":"Trends Parasitol"},{"key":"2026031304531774200_jiaf466-B2","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/s41572-021-00300-2","article-title":"Cholangiocarcinoma","volume":"7","author":"Brindley","year":"2021","journal-title":"Nat Rev Dis 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