Reactivation of Epstein-Barr virus by n-butyric acid from Pseudoramibacter alactolyticus induces inflammatory cytokines in periapical granulomas

Objectives

This study investigates whether latent Epstein-Barr virus (EBV) can be reactivated by n-butyric acid from Pseudoramibacter alactolyticus, and if such reactivation induces expression of interleukin (IL)-1β and IL-6 in periapical granulomas.

Methods

We analyzed periapical granulomas and healthy gingival tissues to detect the presence of EBV and P. alactolyticus. The concentration of n-butyric acid in P. alactolyticus culture supernatants was measured. BZLF-1 luciferase assays were conducted with or without these supernatants. Immunohistochemical detection of ZEBRA-, IL-1β-, and IL-6-expressing cells was performed in the tissue samples. Additionally, mRNA expression levels of BZLF-1, IL-1β, and IL-6 were quantified and statistically analyzed for correlation. The expression of these mRNAs was also measured in Daudi cells treated with or without the culture supernatants.

Results

Both EBV and P. alactolyticus were detected in periapical granulomas, but not in healthy tissues. The concentration of n-butyric acid in the culture supernatants was ∼3.58 mmol/L. BZLF-1 luciferase activity in the presence of the culture supernatants was comparable to that of commercially available butyric acid, whereas no activity was detected without the supernatants. Cells expressing ZEBRA co-expressed IL-1β and IL-6. The mRNA levels of IL-1β and IL-6 in periapical granulomas were correlated with BZLF-1 mRNA levels. Daudi cells treated with the culture supernatants expressed BZLF-1, IL-1β, and IL-6 mRNA, while those without the supernatants did not.

Conclusions

The study concludes that EBV can be reactivated by n-butyric acid produced by P. alactolyticus, leading to the induction of IL-1β and IL-6 expression in periapical granulomas.