期刊
JOURNAL OF VIROLOGY
卷 91, 期 16, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00747-17
关键词
B cell receptor pathway; cyclosporine; dasatinib; Epstein-Barr virus; ibrutinib; idelalisib; lytic infection; rapamycin; tacrolimus; mTOR
类别
资金
- Flight Attendant Medical Research Institute
- Johns Hopkins Institute for Clinical and Translational Research
- National Center for Advancing Translational Sciences (NCATS) [UL1 TR 001079]
- [R21CA188824]
- [R21AI101377]
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.
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