Epstein-Barr Virus Infection in Chronically Inflamed Periapical Granulomas

Abstract

Periapical granulomas are lesions around the apex of a tooth caused by a polymicrobial infection. Treatment with antibacterial agents is normally performed to eliminate bacteria from root canals; however, loss of the supporting alveolar bone is typically observed, and tooth extraction is often selected if root canal treatment does not work well. Therefore, bacteria and other microorganisms could be involved in this disease. To understand the pathogenesis of periapical granulomas more precisely, we focused on the association with Epstein-Barr virus (EBV) using surgically removed periapical granulomas (n = 32). EBV DNA was detected in 25 of 32 periapical granulomas (78.1%) by real-time PCR, and the median number of EBV DNA copies was approximately 8,688.01/μg total DNA. In contrast, EBV DNA was not detected in healthy gingival tissues (n = 10); the difference was statistically significant according to the Mann-Whitney U test (p = 0.0001). Paraffin sections were also analyzed by in situ hybridization to detect EBV-encoded small RNA (EBER)-expressing cells. EBER was detected in the cytoplasm and nuclei of B cells and plasma cells in six of nine periapical granulomas, but not in healthy gingival tissues. In addition, immunohistochemical analysis for latent membrane protein 1 (LMP-1) of EBV using serial tissue sections showed that LMP-1-expressing cells were localized to the same areas as EBER-expressing cells. These data suggest that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas.

Porphyromonas endodontalis reactivates latent Epstein–Barr virus

“…Additionally, a standard curve for EBV was also prepared using 1 × 10 6 DNA copies of EBV, as described previously (Makino et al . ).…”

“…The numbers of EBV DNA copies were determined using a standard curve, as described previously (Makino et al . ). The cell number of P. endodontalis was also determined using a standard curve.…”

“…Expression of EBV‐encoded small RNA (EBER), a reliable marker of EBV infection, has also been detected in periapical granulomas using in situ hybridisation (Makino et al . ). Thus, it was hypothesized that the pathological features of periapical granulomas could be associated with EBV infection.…”

Viral MicroRNAs Identified in Human Dental Pulp

“…Under “healthy” conditions, this indigenous microflora remains benign and assists the host by maintaining basal host immunity, thereby establishing symbiotic association. Influenced by various external and internal factors, however, this equilibrium may be disturbed leading to modulated immune responses (11). …”

“…Ferriera et al reported that 48% of apical abscesses samples had KSHV infections, whereas Chen et al detected HCMV in 29% of the patients with similar disease (12,13). A more recent study suggested that B cells and plasma cells in inflamed granulomas are a major source of EBV infection, and that EBV could play a pivotal role in controlling immune cell responses in periapical granulomas (11). The prevalence of herpesviruses varies across different reports, nonetheless, it is recognized that they may act as opportunistic infections.…”