{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:17:34Z","timestamp":1785363454228,"version":"3.55.0"},"reference-count":125,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Allergy and Infectious Diseases of the National Institutes of Health","award":["R01AI139238"],"award-info":[{"award-number":["R01AI139238"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes significant global morbidity, including fever, rash, and persistent arthralgia. Utilizing untargeted lipidomics, we investigated how CHIKV infection alters host cell lipid metabolism in Vero cells. CHIKV infection induced marked catabolism of hexosylceramides, reducing their levels while increasing ceramide byproducts. Functional studies revealed a reliance on fatty acid synthesis, \u03b2-oxidation, and glycosphingolipid biosynthesis. Notably, inhibition of uridine diphosphate glycosyltransferase 8 (UGT8), essential for galactosylceramide production, significantly impaired CHIKV replication and entry in Vero cells. Sensitivity of CHIKV to UGT8 inhibition was reproduced in a disease-relevant cell line, mouse hepatocytes (Hepa1-6). CHIKV was also sensitive to evacetrapib, a cholesterol ester transfer protein (CETP) inhibitor, though the mechanism of inhibition appeared independent of CETP itself, suggesting an off-target effect. These findings highlight specific lipid pathways, particularly glycosphingolipid metabolism, as critical for CHIKV replication and further refine our understanding of how CHIKV exploits host lipid networks. This study provides new insights into CHIKV biology and suggests that targeted investigation of host lipid pathways may inform future therapeutic strategies.<\/jats:p>","DOI":"10.3390\/v17040509","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T08:21:41Z","timestamp":1743495701000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Chikungunya Replication and Infection Is Dependent upon and Alters Cellular Hexosylceramide Levels in Vero Cells"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2934-8145","authenticated-orcid":false,"given":"Joseph Thomas","family":"Noble","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kingsley","family":"Bimpeh","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7757-2792","authenticated-orcid":false,"given":"Michael Anthony","family":"Pisciotta","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5441-2196","authenticated-orcid":false,"given":"Judith Mary","family":"Reyes Ballista","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Marie","family":"Hines","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-8085","authenticated-orcid":false,"given":"Melinda Ann","family":"Brindley","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"},{"name":"Department of Population Health, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1056\/NEJMra1406035","article-title":"Chikungunya virus and the global spread of a mosquito-borne disease","volume":"372","author":"Weaver","year":"2015","journal-title":"N. 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