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

Abstract

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.

Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review

“…The EBV DNA provokes pro-inflammatory responses via toll-like receptor (TLR) signaling (Salloum et al 2018 ). The EBV DNA can also enhance the expression of IFN-γ, IL-17A and TNF-α in the in vivo colitis model, exacerbating the colon damage (Wu et al 2019 ; Andari et al 2021 ) and leading to increase of disease severity (Kato et al 2021 ). T cells, B cells and NK cells infections also occur, impairing cellular immunity.…”

Association Between Inflammatory Bowel Disease and Viral Infections

“…As a result, it increases the severity of colon damage. These findings indicate that EBV DNA increases pro-inflammatory responses in colitis [42]. Study results showed that EBV infection increases the prevalence of lymphoproliferative disorders in IBD patients after using immunosuppressive drugs [43].…”

Impact of Epstein–Barr virus infection in patients with inflammatory bowel disease

“…Likewise, recent studies formed the same conclusions in cohorts of Chinese patients with IBD (20)(21)(22)(23). In addition to these clinical studies, a recent study using an IBD mouse model, namely, the dextran sodium sulfate (DSS) mouse colitis model, detected that the presence of EBV DNA exacerbated colitis by aggravating colonic disease activity and increasing damage to the colon histologic architecture; this result indicates the possibility of potential therapeutic approaches targeting endosomal Toll-like receptor (TLR) signaling, which needs to be tested in large proportions of patients with IBD (27).…”