Latent Epstein–Barr Virus Infection Correlates with Glycosphingolipid Enrichment and Morphological Remodeling of Extracellular Particles
Epstein–Barr virus (EBV) is causally associated with various malignancies and autoimmune diseases. It establishes a lifelong latent infection in host B-lymphocytes, and can strategically manipulate host cell metabolism and cell-to-cell communication via extracellular particles (EPs). While EBV-induced changes in fatty acid and mevalonate pathways are documented, the role of the sphingolipid network in this process remains poorly understood. In this study, we characterized both the EP and the cellular sphingolipid signatures of three EBV-infected (EBV+) lymphoblastoid cell lines compared to three EBV-negative (EBV−) counterparts. Lipidomic analysis revealed a profound metabolic redirection in EBV+ cells, characterized by reduced ceramide and sphingomyelin levels, and a significant upregulation of glycosphingolipids (GSLs), particularly hexosylceramide and globotrialosylceramide. Furthermore, EBV+ cells released larger, more heterogeneous EPs that are significantly enriched in GSLs and in the viral non-coding RNA EBER1. Our findings suggest that EBV-induced reshaping of sphingolipid metabolism correlates with altered physical properties of the secretome, potentially contributing to viral pathogenesis and microenvironmental manipulation.
Authors
- Monica Miozzo (ORCID: https://orcid.org/0000-0002-6523-4575)
- Raffaella Chiaramonte (ORCID: https://orcid.org/0000-0003-1078-1704)
- Elisa Adele Colombo (ORCID: https://orcid.org/0000-0001-9062-3188)
- Paola Signorelli (ORCID: https://orcid.org/0000-0003-2368-2393)
- Valentina Massa (ORCID: https://orcid.org/0000-0003-2246-9515)
- Michele Dei (ORCID: https://orcid.org/0000-0001-7359-8558)
- Antonino Neri (ORCID: https://orcid.org/0000-0001-9047-5912)
- Alen Zollo (ORCID: https://orcid.org/0009-0005-0908-7469)
- Domenica Giannandrea (ORCID: https://orcid.org/0000-0001-5995-5897)
- Valentina Citro (ORCID: https://orcid.org/0000-0002-0289-404X)
- Alberto Priori (ORCID: https://orcid.org/0000-0002-1549-3851)
- Graziano Serrao (ORCID: https://orcid.org/0000-0001-9651-7685)
- Alessandra Mingione (ORCID: https://orcid.org/0000-0001-8008-0191)
- Filippo Martinelli Boneschi (ORCID: https://orcid.org/0000-0002-9955-1368)
- Cristina Gervasini (ORCID: https://orcid.org/0000-0002-1165-7935)
- Lucia Centofanti (ORCID: https://orcid.org/0009-0000-1301-9390)
- Corinne Monzani (ORCID: https://orcid.org/0009-0006-1136-0521)
- Andrea Corona (ORCID: https://orcid.org/0009-0008-8573-1748)
Institutions
- University of Insubria (IT)
- University of Milan (IT)
- Azienda Sanitaria Unità Locale di Reggio Emilia (IT)
- IRCCS Policlinico San Donato (IT)
Publication Details
- Journal
- Biology
- Published
- 2026-08-18
- DOI
- https://doi.org/10.3390/biology15161421
- Primary Topic
- Viral-associated cancers and disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00