Viruses in Periodontitis: Evidence, Mechanisms, Diagnosis and Therapeutic Implications
Authors
MDS(pursuing) - Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, Uttar Pradesh (India)
Prof. (Dr.) Anjani Kumar Pathak
MDS, FAOI, FISDR, FPFA - Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, Uttar Pradesh (India)
MDS, FADI, FICD, FPFA, AFILD - Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, Uttar Pradesh (India)
MDS, FPFA, FICD - Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, Uttar Pradesh (India)
MDS, MNAMS, FICD, FPFA, AFILD - Department of Periodontology, Faculty of Dental Sciences, King George's Medical University, Lucknow, Uttar Pradesh (India)
Dr. Neetu Rani, MDS (Periodontology), Assistant Professor, King George’s Medical University (KGMU), Lucknow, Uttar Pradesh, India. (India)
Article Information
DOI: 10.51244/IJRSI.2026.1308000352
Subject Category: Medicine
Volume/Issue: 13/8 | Page No: 5448-5457
Publication Timeline
Submitted: 2026-09-07
Accepted: 2026-09-12
Published: 2026-09-26
Abstract
Periodontitis is a biofilm-associated, host-mediated inflammatory disease, but bacterial dysbiosis alone does not fully explain its episodic activity and variable response to treatment. This narrative review evaluates evidence for human herpesviruses and bacteriophages as modifiers of periodontal ecology. Targeted searches of PubMed, PubMed Central and publisher databases were conducted through 31 July 2026. Epstein-Barr virus and human cytomegalovirus are detected more frequently in many deep or active periodontal sites than in healthy sites, although findings vary with population, specimen type and assay. Mechanistic studies support viral effects on cytokine signalling, immune surveillance, epithelial integrity, osteoclastogenesis and viral-bacterial cooperation. Metagenomic studies also identify disease-associated changes in bacteriophage communities. Quantitative polymerase chain reaction is useful for estimating viral burden, but DNA detection alone cannot distinguish latent carriage from active infection. RNA-based assays, tissue localisation and longitudinal sampling are required for stronger causal inference. Mechanical periodontal therapy may reduce viral burden indirectly, whereas evidence for adjunctive antiviral treatment is limited. Current findings support a context-dependent model in which viruses act as ecological or immunological cofactors rather than universal causes of periodontitis. Routine viral testing or antiviral therapy is therefore not justified outside research or carefully selected refractory cases.
Keywords
periodontitis; oral virome; Epstein-Barr virus; cytomegalovirus; bacteriophage; quantitative PCR; antiviral therapy
Downloads
References
1. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018;45 Suppl 20:S162-S170. [Google Scholar] [Crossref]
2. doi:10.1111/jcpe.12946. [Google Scholar] [Crossref]
3. Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis model of periodontal disease etiology. Mol Oral Microbiol. 2012;27(6):409-419. doi:10.1111/j.2041-1014.2012.00663.x. [Google Scholar] [Crossref]
4. Slots J. Herpesviruses in human periodontal disease. J Periodontal Res. 2000;35(1):3-16. [Google Scholar] [Crossref]
5. doi:10.1034/j.1600-0765.2000.035001003.x. [Google Scholar] [Crossref]
6. Contreras A, Zadeh HH, Nowzari H, Slots J. Herpesvirus infection of inflammatory cells in human periodontitis. Oral Microbiol Immunol. 1999;14(4):206-212. doi:10.1034/j.1399-302X.1999.140402.x. [Google Scholar] [Crossref]
7. Kato A, Imai K, Ochiai K, Ogata Y. Higher prevalence of Epstein-Barr virus DNA in deeper periodontal pockets of chronic periodontitis in Japanese patients. PLoS One. 2013;8(8):e71990. doi:10.1371/journal.pone.0071990. [Google Scholar] [Crossref]
8. Maulani C, Auerkari EI, Masulili SLC, Soeroso Y, Santoso WD, Kusdhany LS. Association between Epstein-Barr virus and periodontitis: a meta-analysis. PLoS One. 2021;16(10):e0258109. [Google Scholar] [Crossref]
9. doi:10.1371/journal.pone.0258109. [Google Scholar] [Crossref]
10. Zhu C, Li F, Wong MCM, Feng XP, Lu HX, Xu W. Association between herpesviruses and chronic periodontitis: a meta-analysis based on case-control studies. PLoS One. 2015;10(12):e0144319. doi:10.1371/journal.pone.0144319. [Google Scholar] [Crossref]
11. Li F, Zhu C, Deng FY, Wong MCM, Lu HX, Feng XP. Herpesviruses in etiopathogenesis of aggressive periodontitis: a meta-analysis based on case-control studies. PLoS One. 2017;12(10):e0186373. doi:10.1371/journal.pone.0186373. [Google Scholar] [Crossref]
12. Saygun I, Kubar A, Sahin S, Sener K, Slots J. Quantitative analysis of association between herpesviruses and bacterial pathogens in periodontitis. J Periodontal Res. 2008;43(3):352-359. doi:10.1111/j.1600-0765.2007.01043.x. [Google Scholar] [Crossref]
13. Chen C, Feng P, Slots J. Herpesvirus-bacteria synergistic interaction in periodontitis. Periodontol 2000. 2020;82(1):42-64. doi:10.1111/prd.12311. [Google Scholar] [Crossref]
14. Zeng W, Liu G, Luan Q, Yang C, Luo X, Zhu Z, Yu X. Epstein-Barr virus promotes inflammatory cytokine production in human gingival fibroblasts. Int Dent J. 2024;74(3):607-615. [Google Scholar] [Crossref]
15. doi:10.1016/j.identj.2023.12.006. [Google Scholar] [Crossref]
16. Imai K, Inoue H, Tamura M, Cueno ME, Takeichi O, Kusama K, et al. Epstein-Barr virus promotes inflammatory cytokines and RANKL-induced osteoclast differentiation. Int J Mol Sci. 2022;23(2):809. doi:10.3390/ijms23020809. [Google Scholar] [Crossref]
17. Ly M, Abeles SR, Boehm TK, Robles-Sikisaka R, Naidu M, Santiago-Rodriguez T, et al. Altered oral viral ecology in association with periodontal disease. mBio. 2014;5(3):e01133-14. [Google Scholar] [Crossref]
18. doi:10.1128/mBio.01133-14. [Google Scholar] [Crossref]
19. Chu T, Liu J, Zhang Y, Yang K, Li S, Yan Q, Li Y. Metagenome-based virome analysis identifies oral viral signatures for periodontitis. J Oral Microbiol. 2026;18(1):2662091. [Google Scholar] [Crossref]
20. doi:10.1080/20002297.2026.2662091. [Google Scholar] [Crossref]
21. Martinez A, Kuraji R, Kapila YL. The human oral virome: shedding light on the dark matter. Periodontol 2000. 2021;87(1):282-298. doi:10.1111/prd.12396. [Google Scholar] [Crossref]
22. Emecen-Huja P, Danaher RJ, Dawson DR 3rd, Wang C, Kryscio RJ, Ebersole JL, et al. Relationship between herpesviruses and periodontal disease progression. J Clin Periodontol. 2020;47(4):442-450. doi:10.1111/jcpe.13239. [Google Scholar] [Crossref]
23. Herrero-Sanchez A, Haroyan-Darbinyan E. Prevalence of Epstein-Barr virus, cytomegalovirus, and periodontopathic bacteria in patients with periodontitis: a case-control study. Clin Exp Dent Res. 2025;11:e70084. doi:10.1002/cre2.70084. [Google Scholar] [Crossref]
24. Tonoyan L, Chevalier M, Vincent-Bugnas S, Marsault R, Doglio A. Detection of Epstein-Barr virus in periodontitis: a review of methodological approaches. Microorganisms. 2021;9(1):72. [Google Scholar] [Crossref]
25. doi:10.3390/microorganisms9010072. [Google Scholar] [Crossref]
26. Bostanci N, Manoil D, Van Holm W, Belibasakis GN, Teughels W. Microbial markers for diagnosis and risk assessment for periodontal diseases: a systematic literature search and narrative synthesis. J Clin Periodontol. 2025;52(Suppl 29):125-154. doi:10.1111/jcpe.14183. [Google Scholar] [Crossref]
27. Dong A, Proctor G, Zaric S. Diagnostic accuracy of microbiome-derived biomarkers in periodontitis: systematic review and meta-analysis. J Periodontal Res. 2025;60(8):748-761. doi:10.1111/jre.13377. [Google Scholar] [Crossref]
28. Geng M, Li M, Li Y, Zhu J, Sun C, Wang Y, et al. A universal oral microbiome-based signature for periodontitis. iMeta. 2024;3(4):e212. doi:10.1002/imt2.212. [Google Scholar] [Crossref]
29. Baima G, Dabdoub S, Thumbigere-Math V, Ribaldone DG, Caviglia GP, Tenori L, et al. Multi-omics signatures of periodontitis and periodontal therapy on the oral and gut microbiome. J Periodontal Res. 2025;60(12):1237-1253. doi:10.1111/jre.70055. [Google Scholar] [Crossref]
30. Sunde PT, Olsen I, Enersen M, Grinde B. Patient with severe periodontitis and subgingival Epstein-Barr virus treated with antiviral therapy. J Clin Virol. 2008;42(2):176-178. [Google Scholar] [Crossref]
31. doi:10.1016/j.jcv.2008.01.007. [Google Scholar] [Crossref]
32. Jakovljevic A, Andric M, Jacimovic J, Milasin J, Botero JE. Herpesviruses in periodontitis: an umbrella review. In: Nibali L, ed. Periodontitis: Advances in Experimental Research. Cham: Springer; 2022:107-123. doi:10.1007/978-3-030-96881-6_7. [Google Scholar] [Crossref]
Metrics
Views & Downloads
Similar Articles
- Treasure of 6th Edition of Organon of Medicine- Lm Potency
- Neurobehavioral and Immune-Histochemical Effects of Daucus Carota Ethanolic Leaf Extract in Cadmium-Induced Toxicity of the Hippocampus and Prefrontal Cortex of Adult Wistar Rats
- Unveiling the Antimicrobial Potential of Homoeopathic Sarcode and Bowel Nosode: A Study on Histaminum and Dysenteriae Co against Escherichia Coli And Klebsiella Bacteria
- Incidence of Cardiovascular Events in Patients Receiving Hematopoietic Stem Cell Transplant (HSCT) in HCTM – (A Retrospective Cohort Study)
- A Prospective Case Study Examining the Effectiveness of Homoeopathic Medicine in Treating Degenerative Changes in the Lumbar Spine-A Case Report