4.5 Article

Porphyromonas endodontalis reactivates latent Epstein-Barr virus

Journal

INTERNATIONAL ENDODONTIC JOURNAL
Volume 51, Issue 12, Pages 1410-1419

Publisher

WILEY
DOI: 10.1111/iej.12959

Keywords

BZLF-1; Epstein-Barr virus; n-butyric acid; periapical periodontitis; Porphyromonas endodontalis; ZEBRA

Funding

  1. Japan Society for the Promotion of Science [26462897, 17K11717]
  2. Sato Fund, Nihon University School of Dentistry
  3. Nihon University Multidisciplinary Research Grant for 2017-2018

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Aim To determine whether Porphyromonas endodontalis can reactivate latent Epstein-Barr virus (EBV). Methodology Results The concentrations of short-chain fatty acids (SCFAs) in P. endodontalis culture supernatants were determined using high-performance liquid chromatography. A promoter region of BamHI fragment Z leftward open reading frame 1 (BZLF-1), which is a transcription factor that controls the EBV lytic cycle, was cloned into luciferase expression vectors. Then, the luciferase assay was performed using P. endodontalis culture supernatants. Histone acetylation using Daudi cells treated with P. endodontalis culture supernatants was examined using Western blotting. BZLF-1 mRNA and BamHI fragment Z EB replication activator (ZEBRA) protein were also detected quantitatively using real-time polymerase chain reaction (PCR) and Western blotting. Surgically removed periapical granulomas were examined to detect P. endodontalis, EBV DNA, and BZLF-1 mRNA expression using quantitative real-time PCR. Statistical analysis using Steel tests was performed. The concentrations of n-butyric acid in P. endodontalis culture supernatants were significantly higher than those of other SCFAs (P = 0.0173). Using B-95-8-221 Luc cells treated with P. endodontalis culture supernatants, the luciferase assay demonstrated that P. endodontalis induced BZLF-1 expression. Hyperacetylation of histones was also observed with the culture supernatants. BZLF-1 mRNA and ZEBRA protein were expressed by Daudi cells in a dose-dependent manner after the treatment with P. endodontalis culture supernatants. P. endodontalis and BZLF-1 in periapical granulomas were also detected. The expression levels of BZLF-1 mRNA were similar to the numbers of P. endodontalis cells in each specimen. Conclusions n-butyric acid produced by P. endodontalis reactivated latent EBV.

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