Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts

Zeng, Wenmin; Liu, Guojing; Luan, Qingxian; Yang, Chunyu; Luo, Xin; Zhu, Zijun; Yu, Xiaoqian

doi:10.1016/j.identj.2023.12.006

Cited by 2 publications

(1 citation statement)

References 41 publications

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“…73 In periodontal diseases, P. gingivalis can induce the reactivation of EBV through butyric acid. 74 Facilitating the production of proinflammatory cytokines in gingival fibroblasts and osteoblast differentiation, 75,76 EBV infection also accelerates the progression of periodontal diseases. And the localized inflammatory status in periodontitis in turn provides more chances for EBV infection.…”

Section: F I G U R Ementioning

confidence: 99%

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009−2014

Fang,

Liu,

Mao

et al. 2024

Journal of Medical Virology

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Periodontitis is a cumulative inflammatory disease associated with multiple health conditions and various systemic diseases. As a common disease, virus infection along with its consequences has become a serious health burden. The study aims to evaluate the relationship between common viruses including hepatitis virus, human immunodeficiency virus (HIV), herpes simplex virus (HSV), human papillomavirus (HPV), and periodontitis. The data from the US National Health and Nutrition Examination Survey (NHANES) 2009−2014 was adopted and screened through, including 10 714 participants. Generalized linear regression was conducted to verify the relationships between the virus infections and periodontitis. Moreover, we also performed analyses in age and gender subgroups. The results suggested that the infection of HCV, HSV‐1, and HSV‐2 was significantly associated with the prevalence of periodontitis (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.26−1.70; OR 1.09, 95% CI 1.05−1.13; OR 1.06, 95% CI 1.01 ‐ 1.11, respectively) and risk of developing moderate or severe periodontitis (OR 1.51, 95% CI 1.29−1.77; OR 1.08, 95% CI 1.04−1.12; OR 1.05, 95% CI 1.01−1.10, respectively) after adjusting all relevant co‐factors. Subgroup analyses revealed a steady association between periodontitis and hepatitis C virus (HCV) or HSV‐1 infection, while the relationship between HSV‐2 and HPV infection can also be found in some subgroups. The presence of HCV and HSV infection was found to be significantly associated with the prevalence of periodontitis, including moderate or severe cases. Moreover, the association of periodontitis and HPV infection can also be observed in people < 35 years.

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Section: F I G U R Ementioning

confidence: 99%

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009−2014

Fang,

Liu,

Mao

et al. 2024

Journal of Medical Virology

View full text Add to dashboard Cite

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Appraising the life‐course impact of Epstein‐Barr virus exposure and its genetic signature on periodontitis

Ye,

Yuan,

Bai

et al. 2024

Journal of Periodontology

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BackgroundPeriodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein‐Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship and genetic connection between them remain unknown.MethodsWithin a life‐course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, and reverse MR, to investigate the causal association between EBV exposure and periodontitis. Additionally, linkage disequilibrium score regression and colocalization analysis were utilized to assess the cross‐trait genetic correlations, followed by transcriptome‐wide association and enrichment analysis to discern the genetic‐phenotypic biological profiles.ResultsHeightened levels of EBV antibodies, particularly early antigen diffuses (which serve as indicators of early infection or reactivation), are associated with an increased risk of periodontitis (odds ratio [OR]: 1.27 [1.09–1.47], p = 6.05 × 10−3) and demonstrate a significant genetic correlation (p = 4.11 × 10−3). This pathogenesis may involve the high‐confidence causal gene RNASEK located in 17p13.1. Genetically predicted early‐life anti‐EBV immunoglobulin G (IgG) levels are correlated to a reduced periodontitis risk (OR: 0.89 [0.82–0.97], p = 1.76 × 10−3).ConclusionsThe present study highlights the impact of life‐course EBV exposure and its genetic hallmark on periodontitis, providing novel perspectives into the underlying pathogenesis and management strategies for EBV‐related periodontitis. These findings underscore diverse clinical and public health implications, encompassing antiviral therapies, viral vaccination strategies, and tailored interventions for individualized periodontitis management. Further research is required to validate and expand upon our findings.Plain Language SummaryPeriodontitis is a chronic inflammatory disease driven by interactions between microbial pathogens and the host immune system. While bacteria have traditionally been the focus of research, recent studies highlight the significance of virus‐bacteria interactions, particularly the role of Epstein‐Barr virus (EBV)—a herpesvirus infecting over 90% of the global population—in the development of periodontitis. However, the underlying causal and genetic mechanisms remain unclear. Our study employed genome‐wide multi‐omics approaches to investigate the link between EBV exposure and periodontitis. We found that recent EBV infection or reactivation increases the risk of periodontitis, whereas early‐life exposure, possibly enabling immune resistance, may reduce it. Essential genes were identified as potential mediators, including CRTC3‐AS1, HLA‐DQA1, and RNASEK. These findings provide novel insights into the EBV‐periodontitis connection. For example, viral testing and control could benefit patients unresponsive to standard bacterial treatments, and early viral exposure via vaccination might reduce the risk of periodontitis. Further clinical studies are required to elucidate these underlying mechanisms and the contribution of virus‐bacteria interactions.

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Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts

Cited by 2 publications

References 41 publications

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009−2014

Association between virus infection and periodontitis: Evidence from the National Health and Nutrition Examination Survey 2009−2014

Appraising the life‐course impact of Epstein‐Barr virus exposure and its genetic signature on periodontitis

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