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Ebola virus is known to directly target endothelial cells and macrophages, even without infecting them, through direct interactions with viral proteins. These interactions affect cellular mechanics and immune processes, which are tightly linked to other key cellular functions such as metabolism. However, research regarding metabolic activity of these cells upon viral exposure remains limited, hampering our understanding of its pathophysiology and progression. Therefore, in the present study, an untargeted cellular metabolomic approach was performed to investigate the metabolic alterations of primary human endothelial cells and M1 and M2 macrophages upon exposure to Ebola virus\u2013like particles (VLP). The results show that Ebola VLP led to metabolic changes among endothelial, M1, and M2 cells. Differential metabolite abundance and perturbed signaling pathway analysis further identified specific metabolic features, mainly in fatty acid-, steroid-, and amino acid\u2013related metabolism pathways for all the three cell types, in a host cell specific manner. Taken together, this work characterized for the first time the metabolic alternations of endothelial cells and two primary human macrophage subtypes after Ebola VLP exposure, and identified the potential metabolites and pathways differentially affected, highlighting the important role of those host cells in disease development and progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                    <jats:p>\u2022 Ebola VLP can lead to metabolic alternations in endothelial cells and M1 and M2 macrophages.<\/jats:p>\n                    <jats:p>\u2022 Differential abundance of metabolites, mainly including fatty acids and sterol lipids, was observed after Ebola VLP exposure.<\/jats:p>\n                    <jats:p>\u2022 Multiple fatty acid-, steroid-, and amino acid\u2013related metabolism pathways were observed perturbed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-023-02309-4","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T22:02:30Z","timestamp":1679608950000},"page":"557-568","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Ebola virus\u2013like particles reprogram cellular metabolism"],"prefix":"10.1007","volume":"101","author":[{"given":"Huaqi","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Abouleila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anno","family":"Saris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom H. 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