The role of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in the exacerbation of inflammatory bowel disease (IBD) is still uncertain. We prospectively investigated the presence of EBV and HCMV infection in both epithelial and immune cells of colonic mucosa of IBD patients, both refractory and responders to standard therapies, in comparison with patients suffering from irritable bowel syndrome who were considered as controls, by using quantitative real-time polymerase chain reaction, immunohistochemistry and in situ hybridization, in an attempt to assess viral localization, DNA load, life cycle phase and possible correlation with disease activity indexes. We obtained clear evidence of the presence of high DNA loads of both viruses in either enterocytes or immune cells of refractory IBD patients, whereas we observed low levels in the responder group and an absence of detectable copies in all cell populations of controls. Remarkably, the values of EBV and HCMV DNA in inflamed mucosa were invariably higher than in non-inflamed areas in both IBD groups, and the EBV DNA loads in the cell populations of diseased mucosa of refractory IBD patients positively correlated with the severity of mucosal damage and clinical indexes of activity. Moreover, EBV infection resulted the most prevalent either alone or in combination with HCMV, while immunohistochemistry and in situ hybridization did not allow us to distinguish between the different phases of viral life cycle. Finally, as regards treatment, these novel findings could pave the way for the use of new antiviral molecules in the treatment of this condition.

2nd Department of Internal Medicine St Anne's University Hospital and Masaryk University Pekarska 53 656 91 Brno Czech Republic

Biometry and Clinical Epidemiology Unit IRCCS Policlinico San Matteo Foundation Pavia Italy

Department of Clinical Sciences Surgery Diagnostics and Pediatrics University of Pavia Pavia Italy

Department of Human Pathology IRCCS Policlinico San Matteo Foundation Pavia Italy

Department of Internal Medicine IRCCS Policlinico San Matteo Foundation University of Pavia Piazzale Golgi 19 27100 Pavia Italy

Department of Pharmacology and Toxicology Faculty of Pharmacy Comenius University Odborarov 10 832 32 Bratislava Slovak Republic

SS Virologia Molecolare SC Virologia e Microbiologia IRCCS Policlinico San Matteo Foundation Pavia Italy

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