Alari-Pahissa, ElisendaAtaya Fernández, Michelle, 1993-Moraitis, IliasCampos Ruiz, MiriamAltadill, MireiaMuntasell i Castellví, Aura, 1972-Moles, AnnaLópez-Botet, M. (Miguel)2021-10-202021-10-202021Alari-Pahissa E, Ataya M, Moraitis I, Campos-Ruiz M, Altadill M, Muntasell A, Moles A, López-Botet M. NK cells eliminate Epstein-Barr virus bound to B cells through a specific antibody-mediated uptake. PLoS Pathog. 2021;17(8):e1009868. DOI: 10.1371/journal.ppat.10098681553-7366http://hdl.handle.net/10230/48713Epstein Barr virus (EBV) causes a highly prevalent and lifelong infection contributing to the development of some malignancies. In addition to the key role played by T cells in controlling this pathogen, NK cells mediate cytotoxicity and IFNγ production in response to EBV-infected B cells in lytic cycle, both directly and through antibody (Ab)-dependent activation. We recently described that EBV-specific Ab-dependent NK cell interaction with viral particles (VP) bound to B cells triggered degranulation and TNFα secretion but not B cell lysis nor IFNγ production. In this report we show that NK cell activation under these conditions reduced B cell transformation by EBV. NK cells eliminated VP from the surface of B cells through a specific and active process which required tyrosine kinase activation, actin polymerization and Ca2+, being independent of proteolysis and perforin. VP were displayed at the NK cell surface before being internalized and partially shuttled to early endosomes and lysosomes. VP transfer was encompassed by a trogocytosis process including the EBV receptor CD21, together with CD19 and CD20. Our study reveals a novel facet of the antibody-dependent NK cell mediated response to this viral infection.application/pdfeng© 2021 Alari-Pahissa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.NK cells eliminate Epstein-Barr virus bound to B cells through a specific antibody-mediated uptakeinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1371/journal.ppat.1009868NK cellsB cellsCell stainingEpstein-Barr virusCell degranulationCloningCytotoxicityMonocytesinfo:eu-repo/semantics/openAccess