Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches

Abstract

Periodontitis, an inflammatory condition that affects the structures surrounding the tooth eventually leading to tooth loss, is one of the two biggest threats to oral health. Beyond oral health, it is associated with systemic diseases and even with cancer risk. Obviously, periodontitis represents a major global health problem with significant social and economic impact. Recently, a new paradigm was proposed in the etiopathogenesis of periodontitis involving a herpesviral–bacterial combination to promote long-term chronic inflammatory disease. Periodontitis as a risk factor for other systemic diseases can also be better explained based on viral–bacterial etiology. Significant efforts have brought numerous advances in revealing the links between periodontitis and Epstein–Barr virus (EBV), a gamma herpesvirus ubiquitous in the adult human population. The strong evidence from these studies may contribute to the advancement of periodontitis research and the ultimate control of the disease. Advancing the periodontitis research will require implementing suitable methods to establish EBV involvement in periodontitis. This review evaluates and summarizes the existing methods that allow the detection and diagnosis of EBV in periodontitis (also applicable in a more general way to other EBV-related diseases), and discusses the feasibility of the application of innovative emerging technologies.

The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions

“…A recent study found that latent membrane protein 1, encoded by EBV, induces IL8 production, which promotes the progression of periodontitis in human gingival cells (Watanabe et al, 2019). However, the role of EBV in the etiology of periodontitis has not been clarified (Imai and Ogata, 2020;Tonoyan et al, 2020). In summary, the roles of viruses in oral diseases are extremely important.…”

The roles of DNA methylation on the promotor of the Epstein–Barr virus (EBV) gene and the genome in patients with EBV-associated diseases

“…The transcriptional promoter of LMP (LMPp) is located in the BamH I N region, which is transactivated by EBNA2, and EBNA2 induces the expression of LMPs (Kartika et al 2020). The EBV lytic cycle is initiated by the activation of two promoters, the BZLF1 promoter (Zp) and BRLF1 promoter (Rp), that direct the expression of the immediate-early genes Zta and Rta, which in turn activate the downstream lytic genes individually or coordinately (Jin et al 2010;Tonoyan et al 2020).…”

Multiple cross displacement amplification combined with nanoparticle-based lateral flow biosensor for rapid and sensitive detection of Epstein-Barr virus

“…In tumor biopsy samples, the gold standard technique for detecting latent EBV is in situ hybridization (ISH) using DNA or RNA probes specific to EBV-encoded RNA (EBERs) ( Fanaian et al., 2009 ; AbuSalah et al., 2020 ). Given the abundant expression (in millions of copies) of EBERs in latently-infected cells, they serve as dependable molecular markers crucial for detecting and localizing EBV-infected tissue samples ( AbuSalah et al., 2020 ; Tonoyan et al., 2020 ). Nevertheless, the drawbacks of complex, tedious, and time-consuming procedures with a high possibility of obtaining false negative results restrict its extensive utilization in clinical diagnosis ( AbuSalah et al., 2020 ).…”

“…This method facilitates the real-time monitoring and quantification of amplified targeted nucleic acid sequences by employing either fluorescent probes or an intercalating dye, based on amplifying a conserved sequence. ( AbuSalah et al., 2020 ; Tonoyan et al., 2020 ). Although highly sensitive, specific, and efficient, PCR-based techniques require complex thermal cycling apparatus for target DNA amplification and need gel electrophoresis or probe hybridization techniques for result analysis, hindering its widespread use in resource-limited regions ( Wang et al., 2016a ; Wang et al., 2016b ; Yuan et al., 2020 ).…”