title: Differential cellular localization of Epstein-Barr virus and human cytomegalovirus in the colonic mucosa of patients with active or quiescent inflammatory bowel disease.
abstract: 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.
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy. rachele.ciccocioppo@unipv.it.
authors.forename: Rachele
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Racca
authors.affiliation: Biometry and Clinical Epidemiology Unit, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Luigia
authors.initials: L
authors.lastname: Scudeller
authors.affiliation: SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piralla
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Formagnana
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Lodovica
authors.initials: L
authors.lastname: Pozzi
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Betti
authors.affiliation: Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.affiliation: Department of Human Pathology, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Riboni
authors.affiliation: 2nd Department of Internal Medicine, St. Anne's University Hospital and Masaryk University, Pekarska 53, 656 91, Brno, Czech Republic. peter.kruzliak@savba.sk.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odborarov 10, 832 32, Bratislava, Slovak Republic. peter.kruzliak@savba.sk.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: SS Virologia Molecolare - SC Virologia e Microbiologia, IRCCS Policlinico San Matteo Foundation, Pavia, Italy.|Department of Clinical Sciences, Surgery, Diagnostics and Pediatrics, University of Pavia, Pavia, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Baldanti
authors.affiliation: Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, University of Pavia, Piazzale Golgi, 19, 27100, Pavia, Italy.
authors.forename: Gino Roberto
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D000328:Adult; D003106:Colon / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D018450:Disease Progression; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000821:virology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult
keywords: Enterocytes; Inflammatory bowel disease; Mucosa; Quantitative real-time PCR; Viral infection