Anti-TNF[alpha] therapy for inflammatory bowel diseases is associated with Epstein-Barr virus lytic activation

• Published in: Journal of medical virology 2016-02, Vol.88 (2), p.312
• Main Authors: Lapsia, Sameer, Koganti, Siva, Spadaro, Salvatore, Rajapakse, Ramona, Chawla, Anupama, Bhaduri-McIntosh, Sumita
• Format: Article
• Language: English
• Subjects: Antiviral drugs; Inflammatory bowel disease; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.24331

Anti-TNF[alpha] therapy, known to suppress T-cell immunity, is increasingly gaining popularity for treatment of autoimmune diseases including inflammatory bowel diseases (IBD). T-cell suppression increases the risk of B-cell EBV-lymphoproliferative diseases and lymphomas. Since EBV-lytic activation is essential for development of EBV-lymphomas and there have been reports of EBV-lymphomas in patients treated with anti-TNF[alpha] therapy, we investigated if patients treated with anti-TNF[alpha] antibodies demonstrate greater EBV-lytic activity in blood. Peripheral blood mononuclear cells from 10 IBD patients solely on anti-TNF[alpha] therapy compared to 3 control groups (10 IBD patients not on immunosuppressive therapy, 10 patients with abdominal pain but without IBD, and 10 healthy subjects) were examined for the percentage of T-cells, EBV load and EBV-lytic transcripts. Patients on anti-TNF[alpha] therapy had significantly fewer T-cells, greater EBV load, and increased levels of transcripts from EBV-lytic genes of all kinetic classes compared to controls. Furthermore, exposure of EBV-infected B-cell lines to anti-TNF[alpha] antibodies resulted in increased levels of BZLF1 mRNA; BZLF1 encodes for ZEBRA, the viral latency-to-lytic cycle switch. Thus, IBD patients treated with anti-TNF[alpha] antibodies have greater EBV loads likely due to enhanced EBV-lytic gene expression and anti-TNF[alpha] antibodies may be sufficient to activate the EBV lytic cycle. Findings from this pilot study lay the groundwork for additional scientific and clinical investigation into the effects of anti-TNF[alpha] therapy on the life cycle of EBV, a ubiquitous oncovirus that causes lymphomas in the setting of immunocompromise. J. Med. Virol. 88:312-318, 2016. © 2015 Wiley Periodicals, Inc.