Abstract
Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib.
Original language | English (US) |
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Article number | e00747-17 |
Journal | Journal of virology |
Volume | 91 |
Issue number | 16 |
DOIs | |
State | Published - Aug 1 2017 |
Keywords
- B cell receptor pathway
- Cyclosporine
- Dasatinib
- Epstein-Barr virus
- Ibrutinib
- Idelalisib
- Lytic infection
- MTOR
- Rapamycin
- Tacrolimus
ASJC Scopus subject areas
- Microbiology
- Immunology
- Insect Science
- Virology