Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease

Infection with EBV has been associated with various inflammatory disorders including inflammatory bowel diseases (IBD). Contribution of this virus to intestinal disease processes has not been assessed. We previously detected that EBV DNA triggers proinflammatory responses via the activation of endos...

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Main Authors: Sirine Andari, Hadi Hussein, Sukayna Fadlallah, Abdo R. Jurjus, Margret Shirinian, Jana G. Hashash, Elias A. Rahal
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/7/1272
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author Sirine Andari
Hadi Hussein
Sukayna Fadlallah
Abdo R. Jurjus
Margret Shirinian
Jana G. Hashash
Elias A. Rahal
author_facet Sirine Andari
Hadi Hussein
Sukayna Fadlallah
Abdo R. Jurjus
Margret Shirinian
Jana G. Hashash
Elias A. Rahal
author_sort Sirine Andari
collection DOAJ
description Infection with EBV has been associated with various inflammatory disorders including inflammatory bowel diseases (IBD). Contribution of this virus to intestinal disease processes has not been assessed. We previously detected that EBV DNA triggers proinflammatory responses via the activation of endosomal Toll-like receptor (TLR) signaling. Hence, to examine the colitogenic potential of EBV DNA, we used the dextran sodium sulfate (DSS) mouse colitis model. C57BL/6J mice received either DSS-containing or regular drinking water. Mice were then administered EBV DNA by rectal gavage. Administration of EBV DNA to the DSS-fed mice aggravated colonic disease activity as well as increased the damage to the colon histologic architecture. Moreover, we observed enhanced expression of IL-17A, IFNγ and TNFα in colon tissues from the colitis mice (DSS-treated) given the EBV DNA compared to the other groups. This group also had a marked decrease in expression of the CTLA4 immunoregulatory marker. On the other hand, we observed enhanced expression of endosomal TLRs in colon tissues from the EBV DNA-treated colitis mice. These findings indicate that EBV DNA exacerbates proinflammatory responses in colitis. The ubiquity of EBV in the population indicates that possible similar responses may be of pertinence in a relevant proportion of IBD patients.
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spelling doaj.art-30f08e02a0864c008c4e6880af0e11c72023-12-03T13:18:09ZengMDPI AGViruses1999-49152021-06-01137127210.3390/v13071272Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel DiseaseSirine Andari0Hadi Hussein1Sukayna Fadlallah2Abdo R. Jurjus3Margret Shirinian4Jana G. Hashash5Elias A. Rahal6Department of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonDepartment of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, LebanonDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonDivision of Gastroenterology, American University of Beirut Medical Center, Beirut, LebanonDepartment of Experimental Pathology, Immunology and Microbiology, American University of Beirut, Beirut, LebanonInfection with EBV has been associated with various inflammatory disorders including inflammatory bowel diseases (IBD). Contribution of this virus to intestinal disease processes has not been assessed. We previously detected that EBV DNA triggers proinflammatory responses via the activation of endosomal Toll-like receptor (TLR) signaling. Hence, to examine the colitogenic potential of EBV DNA, we used the dextran sodium sulfate (DSS) mouse colitis model. C57BL/6J mice received either DSS-containing or regular drinking water. Mice were then administered EBV DNA by rectal gavage. Administration of EBV DNA to the DSS-fed mice aggravated colonic disease activity as well as increased the damage to the colon histologic architecture. Moreover, we observed enhanced expression of IL-17A, IFNγ and TNFα in colon tissues from the colitis mice (DSS-treated) given the EBV DNA compared to the other groups. This group also had a marked decrease in expression of the CTLA4 immunoregulatory marker. On the other hand, we observed enhanced expression of endosomal TLRs in colon tissues from the EBV DNA-treated colitis mice. These findings indicate that EBV DNA exacerbates proinflammatory responses in colitis. The ubiquity of EBV in the population indicates that possible similar responses may be of pertinence in a relevant proportion of IBD patients.https://www.mdpi.com/1999-4915/13/7/1272inflammatory bowel diseaseEpstein–Barr virusIL-17AToll-like Receptors
spellingShingle Sirine Andari
Hadi Hussein
Sukayna Fadlallah
Abdo R. Jurjus
Margret Shirinian
Jana G. Hashash
Elias A. Rahal
Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
Viruses
inflammatory bowel disease
Epstein–Barr virus
IL-17A
Toll-like Receptors
title Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
title_full Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
title_fullStr Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
title_full_unstemmed Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
title_short Epstein–Barr Virus DNA Exacerbates Colitis Symptoms in a Mouse Model of Inflammatory Bowel Disease
title_sort epstein barr virus dna exacerbates colitis symptoms in a mouse model of inflammatory bowel disease
topic inflammatory bowel disease
Epstein–Barr virus
IL-17A
Toll-like Receptors
url https://www.mdpi.com/1999-4915/13/7/1272
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