Epstein-Barr virus reactivation by persistent apical periodontal pathogens

Area of Science:

• Oral microbiology
• Virology
• Immunology

Background:

• Persistent apical periodontitis is associated with specific microbial communities.
• Epstein-Barr virus (EBV) is a common human herpesvirus with a latent phase.
• The link between oral microbes and EBV reactivation is not fully understood.

Purpose of the Study:

• To investigate if microbes associated with apical periodontitis can trigger Epstein-Barr virus (EBV) reactivation.
• To identify specific microbial species responsible for EBV reactivation in vitro and ex vivo.

Main Methods:

• Analysis of human periapical granulomas and healthy gingival tissues for EBV and specific microbes.
• Quantification of EBV DNA and microbial load using real-time PCR.
• Assessment of EBV gene and protein expression (BZLF-1, LMP-1, ZEBRA) via PCR and immunofluorescence.
• Measurement of microbial n-butyric acid production and in vitro assays with bacterial lysates and cell cultures.

Main Results:

• EBV DNA and BZLF-1 mRNA were detected in 47/50 periapical granulomas.
• Fusobacterium nucleatum load significantly correlated with BZLF-1 expression.
• F. nucleatum, but not other tested microbes like Enterococcus faecalis or Candida albicans, induced EBV reactivation markers (BZLF-1 mRNA, ZEBRA protein) in cell cultures.
• B cells in granulomas expressed EBV proteins LMP-1 and ZEBRA.

Conclusions:

• Fusobacterium nucleatum is a potent reactivator of latent EBV among microbes associated with apical periodontitis.
• This finding suggests a potential mechanism linking persistent oral infections to EBV reactivation.
• Enterococcus faecalis, Candida albicans, and other tested microbes did not show EBV reactivation potential.