NK cells eliminate Epstein-Barr virus bound to B cells through a specific antibody-mediated uptake
Alari Pahissa, Elisenda (Universitat Pompeu Fabra)
Ataya, Michelle (Universitat Pompeu Fabra)
Moraitis, Ilias (University of Ioannina, Ioannina, Greece)
Campos-Ruiz, Miriam (Universitat Pompeu Fabra)
Altadill, Mireia (Universitat Pompeu Fabra)
Muntasell i Castellví, Aura 1972- (Universitat Autònoma de Barcelona)
Moles, Anna (Hospital del Mar (Barcelona, Catalunya))
López-Botet, Miguel (Hospital del Mar (Barcelona, Catalunya))

Data:	2021
Resum:	Epstein 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. Epstein-Barr virus (EBV) is a member of the herpesvirus family which causes a frequent and lifelong infection. The immune system is unable to fully eliminate the virus, which remains dormant in infected B lymphocytes. EBV reactivation leads to the production of new infective particles, spreading to other cells and favoring its transmission. EBV infection goes generally unnoticed in healthy individuals, though it may occasionally cause a disease termed Infectious Mononucleosis, as well as severe disorders in patients with a defective immune response. Remarkably, EBV has oncogenic potential contributing to the development of some tumors, and has been associated to autoimmune diseases. T lymphocytes and Natural Killer (NK) cells play an essential role in the defense against EBV, killing infected cells when the virus reactivates. Antiviral NK cell functions may be also triggered by antibodies (Ab) recognizing infected cells. In this report we provide the first evidence supporting that NK cells in combination with anti-EBV Ab are able to eliminate the virus attached to the surface of B cells, reducing their infection without killing them.
Ajuts:	Agencia Estatal de Investigación SAF2016-80363-C2-1-R Agencia Estatal de Investigación PID2019-110609RB-C21
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PLOS pathogens, Vol. 17 (august 2021) , ISSN 1553-7374

DOI: 10.1371/journal.ppat.1009868
PMID: 34415956

23 p, 3.1 MB

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