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

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.

Periodontal inflammation as a potential driver of HIV low level viremia.

HIV can be successfully suppressed to undetectable levels by antiretroviral therapy (ART) in most people with HIV (PWH). However, a small proportion continues to have persistent low-level viremia (LLV) during ART. A presumed source of LLV is production or replication from viral reservoirs, which are maintained in the presence of ART. It is unknown whether the oral cavity can be considered an HIV reservoir. As periodontal inflammation is a common problem in PWH, we hypothesize that periodontal inflammation in the oral cavity activates (latently) infected cells and thus might be associated with LLV. We included 11 individuals with HIV LLV, and compared HIV-RNA levels in saliva and plasma at baseline and at week 24 after switch of ART. We compared the LLV-group at baseline with 11 age-matched controls with suppressed viremia. To investigate the severity of periodontitis we used Periodontal Inflamed Surface Areas (PISA) by measuring probing depth, gingival recession, bleeding on probing and clinical attachment level. Severity of periodontitis was classified according to the CDC-AAP case definition. Additional insights in periodontal inflammation were obtained by comparing immune activation markers and the presence of periodontal pathogens. In four individuals of the LLV group, residual levels of HIV-RNA were detected in saliva at baseline (N = 1) or at week 24 (N = 2) or both (N = 1). Of the four individuals with LLV, three had residual levels of HIV-RNA in saliva. All 22 individuals had moderate to severe periodontitis. PISA was not significantly different between cases with LLV and controls. Similarly, periodontal pathogens were frequently observed in both groups. Total activated HLA-DR+CD38+ CD4+ cells and CD8+ cells were significantly higher in the LLV group than in the control group (p = <0.01). No immune markers were associated with LLV. In conclusion, periodontal inflammation is an unlikely driver of HIV LLV compared to HIV suppressed individuals.

Human immunodeficiency virus and oral microbiota: mutual influence on the establishment of a viral gingival reservoir in individuals under antiretroviral therapy.

The role of the oral microbiota in the overall health and in systemic diseases has gained more importance in the recent years, mainly due to the systemic effects that are mediated by the chronic inflammation caused by oral diseases, such as periodontitis, through the microbial communities of the mouth. The chronic infection by the human immunodeficiency virus (HIV) interacts at the tissue level (e.g. gut, genital tract, brain) to create reservoirs; the modulation of the gut microbiota by HIV infection is a good example of these interactions. The purpose of the present review is to assess the state of knowledge on the oral microbiota (microbiome, mycobiome and virome) of HIV-infected patients in comparison to that of HIV-negative individuals and to discuss the reciprocal influence of HIV infection and oral microbiota in patients with periodontitis on the potential establishment of a viral gingival reservoir. The influence of different clinical and biological parameters are reviewed including age, immune and viral status, potent antiretroviral therapies, smoking, infection of the airway and viral coinfections, all factors that can modulate the oral microbiota during HIV infection. The analysis of the literature proposed in this review indicates that the comparisons of the available studies are difficult due to their great heterogeneity. However, some important findings emerge: (i) the oral microbiota is less influenced than that of the gut during HIV infection, although some recurrent changes in the microbiome are identified in many studies; (ii) severe immunosuppression is correlated with altered microbiota and potent antiretroviral therapies correct partially these modifications; (iii) periodontitis constitutes a major factor of dysbiosis, which is exacerbated in HIV-infected patients; its pathogenesis can be described as a reciprocal reinforcement of the two conditions, where the local dysbiosis present in the periodontal pocket leads to inflammation, bacterial translocation and destruction of the supporting tissues, which in turn enhances an inflammatory environment that perpetuates the periodontitis cycle. With the objective of curing viral reservoirs of HIV-infected patients in the future years, it appears important to develop further researches aimed at defining whether the inflamed gingiva can serve of viral reservoir in HIV-infected patients with periodontitis.

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

BACKGROUND: Periodontitis is one of the most common chronic oral inflammatory diseases. Over the past decade, herpes viruses, particularly Epstein-Barr virus (EBV), have been considered promising pathogenic candidates for periodontitis. However, the specific mechanism by which EBV contributes to the development of periodontitis is still unknown. This study aimed to explore the mechanism of EBV underlying the inflammatory response in human gingival fibroblasts (HGFs). MATERIALS AND METHODS: HGFs were stimulated with different concentrations of EBV (104, 105, 106, 107, and 108 DNA copies/mL) for 0, 8, 24, or 48 hours. The mRNA levels of interleukin (IL)-1ß, tumour necrosis factor-α (TNF-α), IL-8, monocyte chemoattractant protein-1 (MCP-1), and Toll-like receptor 9 (TLR9) were measured using quantitative real-time polymerase chain reaction (PCR). Enzyme-linked immunosorbent assays (ELISAs) were performed for determining the mRNA and protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Real-time PCR and ELISA were performed to determine the protein levels of IL-1ß, TNF-α, IL-8, and MCP-1. Activation of the TLR9/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa B (NF-κB) pathway was evaluated using western blotting. RESULTS: The expressions of IL-1ß, TNF-α, IL-8, and MCP-1 were significantly upregulated in HGFs under EBV stimulation in a concentration- and time-dependent manner. EBV promoted TLR9 and MyD88 expression and induced NF-κB transcription. On the contrary, the upregulation of these factors and the activation of NF-κB pathway were drastically inhibited by TLR9 antagonists. CONCLUSIONS: Our findings demonstrate that EBV promotes the production of inflammatory cytokines IL-1ß and TNF-α and chemokines IL-8 and MCP-1 in HGFs through the TLR9/MyD88/NF-κB pathway.

Association between human herpes simplex virus and periodontitis: results from the continuous National Health and Nutrition Examination Survey 2009-2014.

BACKGROUND: Periodontitis is a common chronic oral disease which seriously affects people's quality of life. Although human herpes simplex virus (HSV) is also found in periodontal lesions, the association between HSV infection and periodontitis is unclear. METHODS: The National Health and Nutrition Examination Survey (NHANES) data for 2009-2010, 2011-2012 and 2013-2014 was combined, and the association between HSV infection and periodontitis in the general population and particular subgroups was investigated through weighted multi-logistic analyses. RESULTS: There were 4,733 participants aged 30-50 years old with clinically assessed periodontitis concurrent with HSV infection. In general analysis, after adjusted for covariates, both HSV-1 (OR = 1.09, P < 0.001) and HSV-2 (OR = 1.06, P = 0.030) infection was significantly associated with periodontitis. In subgroup analyses, compared with patients without HSV infection, patients with HSV-1( +) & HSV-2( +) and HSV-1( +) & HSV-2(-) infection showed higher risk of periodontitis in all subgroups (OR = 1.15, OR = 1.09, P < 0.001), while patients with HSV-1(-) & HSV-2( +) infection showed higher risk of and periodontitis only in the subgroup of people aged 40-50 years (OR = 1.10, P = 0.032) and the Mexican-American subgroup (OR = 1.35, P = 0.042). When only severe periodontitis is considered, HSV infection was associated with periodontitis, no matter the patient was infected with either of the virus or both. CONCLUSIONS: HSV-1 infection was significantly associated with periodontitis and severe periodontitis, while HSV-2 infection was associated with severe periodontitis, and periodontitis in 40-50-year-olds and Mexican-Americans.

Association between Epstein-Barr virus and periodontitis: A meta-analysis.

PURPOSE: Previous studies have found that Epstein-Barr virus (EBV) is associated with periodontitis, though some controversy remains. This meta-analysis aimed to clarify and update the relationship between EBV and periodontitis as well as clinical parameters. METHODS: A comprehensive search was conducted in the PubMed and Scopus databases in December 2020. Original data were extracted according to defined inclusion and exclusion criteria. Outcomes were analyzed, including overall odds ratios (ORs) and 95% confidence intervals (CIs). A random-effects model was used, and publication bias was assessed by Egger's and Begg's tests. Sensitivity analysis was used to evaluate the stability of the outcome. RESULTS: Twenty-six studies were included in the present meta-analysis, involving 1354 periodontitis patients and 819 healthy controls. The included studies mostly showed high quality. The overall quantitative synthesis for the association between EBV and periodontitis was an increased odds ratio when subgingival EBV was detected OR = 7.069, 95% CI = 4.197-11.905, P<0.001). The results of subgroup analysis suggested that the association of EBV with periodontitis was significant in Asian, European, and American populations (P<0.001; P = 0.04; P = 0.003, respectively) but not in African populations (P = 0.29). Subgroup analysis by sample type showed that subgingival plaque (SgP), tissue and gingival crevicular fluid GCF were useful for EBV detection (P<0.001). EBV detection amplification methods included nested PCR, multiplex PCR and PCR (P<0.001; P = 0.05, P<0.001, respectively), but EBV detection by real-time PCR and loop-mediated isothermal amplification presented no significant result (P = 0.06; P = 0.3, respectively). For the clinical parameters of periodontitis, pocket depth (PD) and bleeding of probing (BOP) percentages were higher in the EBV-positive sites than in the EBV-negative sites (MD 0.47 [0.08, 0.85], P = 0.02; MD 19.45 [4.47, 34.43], P = 0.01). CONCLUSIONS: A high frequency of EBV detection is associated with an increased risk of periodontitis. The EBV association was particularly significant in all populations except in African populations. Subgigival plaque (SgP), tissue and GCF were not significantly different useful material for detecting EBV in periodontitis. Nested PCR and multiplex PCR are reliable methods for this purpose. In the presence of EBV, PD and BOP are reliable clinical parameters for gingival inflammation. However, some caution in such interpretation is justified due to heterogeneity among studies. A suggested extension could assess the parallel influence of other human herpesviruses.

Redondovirus Diversity and Evolution on Global, Individual, and Molecular Scales.

Redondoviridae is a newly established family of circular Rep-encoding single-stranded (CRESS) DNA viruses found in the human ororespiratory tract. Redondoviruses were previously found in ∼15% of respiratory specimens from U.S. urban subjects; levels were elevated in individuals with periodontitis or critical illness. Here, we report higher redondovirus prevalence in saliva samples: four rural African populations showed 61 to 82% prevalence, and an urban U.S. population showed 32% prevalence. Longitudinal, limiting-dilution single-genome sequencing revealed diverse strains of both redondovirus species (Brisavirus and Vientovirus) in single individuals, persistence over time, and evidence of intergenomic recombination. Computational analysis of viral genomes identified a recombination hot spot associated with a conserved potential DNA stem-loop structure. To assess the possible role of this site in recombination, we carried out in vitro studies which showed that this potential stem-loop was cleaved by the virus-encoded Rep protein. In addition, in reconstructed reactions, a Rep-DNA covalent intermediate was shown to mediate DNA strand transfer at this site. Thus, redondoviruses are highly prevalent in humans, found in individuals on multiple continents, heterogeneous even within individuals and encode a Rep protein implicated in facilitating recombination. IMPORTANCERedondoviridae is a recently established family of DNA viruses predominantly found in the human respiratory tract and associated with multiple clinical conditions. In this study, we found high redondovirus prevalence in saliva from urban North American individuals and nonindustrialized African populations in Botswana, Cameroon, Ethiopia, and Tanzania. Individuals on both continents harbored both known redondovirus species. Global prevalence of both species suggests that redondoviruses have long been associated with humans but have remained undetected until recently due to their divergent genomes. By sequencing single redondovirus genomes in longitudinally sampled humans, we found that redondoviruses persisted over time within subjects and likely evolve by recombination. The Rep protein encoded by redondoviruses catalyzes multiple reactions in vitro, consistent with a role in mediating DNA replication and recombination. In summary, we identify high redondovirus prevalence in humans across multiple continents, longitudinal heterogeneity and persistence, and potential mechanisms of redondovirus evolution by recombination.

The feasibility of phage therapy for periodontitis.

Periodontitis, a chronic progressive inflammation caused by plaque biofilm, is the main cause of tooth loss in adults. For certain refractory periodontitis cases, it is difficult to achieve a good curative effect using the existing periodontal treatment approaches, which may be due to periodontal pathogenic mechanism in the affected periodontal tissue that the host cannot resist and eliminate. Various pieces of evidence collectively revealed that most studies are focusing on phages in periodontal disease. Several studies have reported periodontitis treatment using phage therapy, highlighting its features including specificity, rapid propagation, and effectiveness on bacteriophage biofilms. In this study, we focus on these reports, aiming to lay the foundation for improved periodontal treatment approaches.

Nexus between COVID-19 and periodontal disease.

Over the past several decades, studies have demonstrated the existence of bi-directional relationships between periodontal disease and systemic conditions. Periodontitis is a polymicrobial and multifactorial disease involving both host and environmental factors. Tissue destruction is primarily associated with hyperresponsiveness of the host resulting in release of inflammatory mediators. Pro-inflammatory cytokines play a major role in bacterial stimulation and tissue destruction. In addition, these cytokines are thought to underlie the associations between periodontitis and systemic conditions. Current research suggests that increased release of cytokines from host cells, referred to as the cytokine storm, is associated with disease progression in patients with coronavirus disease 2019 (COVID-19). An intersection between periodontitis and pulmonary disease is biologically plausible. Hence, we reviewed the evidence linking COVID-19, cytokines, and periodontal disease. Plaque control is essential to prevent exchange of bacteria between the mouth and the lungs, reducing the risk of lung disease. Understanding these associations may help identify individuals at high risk and deliver appropriate care at early stages.

Comparing the sub-gingival levels of Cytomegalovirus, Epstein-Barr virus, Porphyromonas gingivalis in human immunodeficiency virus-1 seropositive patients with and without antiretroviral therapy.

OBJECTIVES: The effect of antiretroviral therapy (ART) on the oral pathogenic microbes in human immunodeficiency virus-1 seropositive patients remains relatively unexplored. Thus, the present study assessed the effect of ART on the sub-gingival levels of 3 pathogenic microbes. MATERIALS AND METHODS: The study groups consisted of 60 human immunodeficiency virus-1 seropositive patients divided into 3 groups of 20 each. Group 1 had periodontitis and did not start with the ART. Group 2 had periodontitis and started with ART (Tenofovir Disoproxil Fumarate 300 mg + Lamivudine 300 mg + Efavirenz 600 mg) at least 6 months before the study. Group 3 with normal periodontium, and have not started ART. The sub-gingival loads of Cytomegalovirus, Epstein-Barr virus, and the Porphyromonas gingivalis levels were assessed, along with the CD4 counts. RESULTS: The cytomegalovirus load was highest in group 1, followed by groups 2, and 3 (p-value of 0.271). The Epstein-Barr load was highest for group 2, followed by group 3, and 1 (p-value of 0.022). The P.gingivalis load was highest in group 2, followed by groups 1 and 3, (p-value of 0.028). The Epstein-Barr and Cytomegalovirus counts were significantly higher (p-value < 0.02) when the CD4 counts were less than 500 cells/cu3. CONCLUSION: ART did not cause any significant reduction in the sub-gingival levels of any of the 3 examined microbes. Given the lack of any significant effect on the sub-gingival microbial loads by the ART, human immunodeficiency virus patients may require additional anti-microbial agents and regular mechanical plaque removal to maintain their periodontal status.

Oral human cytomegalovirus prevalence and its relationships with periodontitis and Porphyromonas gingivalis in Japanese adults: a cross-sectional study.

OBJECTIVE: This study aimed to clarify the association between oral human cytomegalovirus (HCMV) and periodontitis in Japanese adults. METHODOLOGY: In total, 190 patients (75 men and 115 women; mean age, 70.2 years) who visited Hiroshima University Hospital between March 2018 and May 2020 were included. Oral rinse samples were taken to examine the presence of HCMV DNA using real-time polymerase chain reaction (PCR). P. gingivalis was detected by semi-quantitative PCR analysis. RESULTS: HCMV DNA was present in nine of 190 patients (4.7%). There were significant associations between HCMV presence and the presence of ≥4-mm-deep periodontal pockets with bleeding on probing (BOP) (P<0.01) and ≥6-mm-deep periodontal pockets with BOP (P=0.01). However, no significant relationship was observed between HCMV presence and periodontal epithelial surface area scores. Logistic regression analysis revealed that the presence of ≥4-mm-deep periodontal pockets with BOP was significantly associated with HCMV (odds ratio, 14.4; P=0.01). Propensity score matching was performed between patients presenting ≥4-mm-deep periodontal pockets with BOP (i.e., active periodontitis) and patients without ≥4-mm-deep periodontal pockets with BOP; 62 matched pairs were generated. Patients who had ≥4-mm-deep periodontal pockets with BOP showed a higher rate of HCMV presence (9.7%) than those who lacked ≥4-mm-deep periodontal pockets with BOP (0.0%). There was a significant relationship between HCMV presence and ≥4-mm-deep periodontal pockets with BOP (P=0.03). A significant relationship was found between HCMV/P. gingivalis DNA presence and ≥4-mm-deep periodontal pockets with BOP (P=0.03). CONCLUSIONS: Coinfection of oral HCMV and P. gingivalis was significantly associated with active periodontitis. Moreover, interactions between oral HCMV and P. gingivalis may be related to the severity of periodontal disease.

Proteome Analysis of Molecular Events in Oral Pathogenesis and Virus: A Review with a Particular Focus on Periodontitis.

Some systemic diseases are unquestionably related to periodontal health, as periodontal disease can be an extension or manifestation of the primary disease process. One example is spontaneous gingival bleeding, resulting from anticoagulant treatment for cardiac diseases. One important aspect of periodontal therapy is the care of patients with poorly controlled disease who require surgery, such as patients with uncontrolled diabetes. We reviewed research on biomarkers and molecular events for various diseases, as well as candidate markers of periodontal disease. Content of this review: (1) Introduction, (2) Periodontal disease, (3) Bacterial and viral pathogens associated with periodontal disease, (4) Stem cells in periodontal tissue, (5) Clinical applications of mass spectrometry using MALDI-TOF-MS and LC-MS/MS-based proteomic analyses, (6) Proteome analysis of molecular events in oral pathogenesis of virus in GCF, saliva, and other oral Components in periodontal disease, (7) Outlook for the future and (8) Conclusions. This review discusses proteome analysis of molecular events in the pathogenesis of oral diseases and viruses, and has a particular focus on periodontitis.

COVID-19 & Periodontitis: The cytokine connection.

COVID-19 is now recognized as a pandemic throughout the world, leading to a scramble in order to gather knowledge as well as evidence regarding the 'novel' corona virus which causes this disease. Chemokines are a family of cytokines which are chemotactic in nature and cause the recruitment of cells of inflammation. Periodontitis has long been attributed to having its pathophysiology rooted in a cytokine response. The recent COVID-19 pandemic has been reported to have adverse outcomes related to the establishment of a cytokine storm, many of the components of which are common with the cytokine expression profile of periodontitis. This communication explores the connection between COVID-19 and periodontal disease through their cytokine connection to form a translational basis for recommending maintenance of oral hygiene in the COVID era and to red flag patients with periodontitis as having an increased risk of exhibiting COVID related adverse outcomes.

Salivary markers of oxidative stress and periodontal pathogens in patients with periodontitis from Santander, Colombia. / Marcadores salivales de estrés oxidativo y agentes patógenos periodontales en pacientes con periodontitis en Santander, Colombia

INTRODUCTION: Periodontitis affects more than 20% of the Latin American population. Oxidative markers are associated with greater progression of periodontitis; therefore, its role in pathogenesis should be studied. OBJECTIVE: To determine the prevalence of the main oral bacteria and viruses associated with periodontitis and estimate the total antioxidant capacity and lipid peroxidation in saliva from patients with periodontitis. MATERIALS AND METHODS: We conducted systemically a cross-sectional study in 101 healthy subjects, 87 of whom had been diagnosed with periodontitis (P), according to the criteria of the Centers of Disease Control and Prevention and the American Academy of Periodontology, and 14 without periodontal pockets as controls (C). In subgingival samples, major viruses and dental pathogenic bacteria were identified using PCR techniques. The levels of total antioxidant capacity and malon-di-aldehyde (MDA) were determined by spectrophotometry in samples of unstimulated saliva. RESULTS: The mean of periodontal depth pocket and clinical attachment loss in patients with periodontitis was 5.6 ± 1.7 and 6.1 ± 3.1 mm, respectively. The most prevalent microorganisms were Aggregatibacter actinomycetemcomitans (32.5%) and Porphyromonas gingivalis (18.6%). The patients from rural areas showed a higher percentage of A. actinomycetemcomitans (urban: 17.9% vs. rural: 48.9%, p=0.0018). In patients with periodontitis, the frequency of EBV, HSV1 and 2, and HCMV genes was 2.3%. Periodontitis patients had higher levels of MDA (P: 2.1 ± 1.5; C: 0.46 ± 0.3 µmol/g protein; p=0.0001) and total antioxidant capacity (P: 0.32 ± 0.2; C: 0.15 ± 0.1 mM; p< 0.0036). Oxidative markers showed no modifications due to the presence of periodontopathic bacteria. CONCLUSIONS: Aggregatibacter actinomycetemcomitans was the most prevalent bacteria; its presence did not modify the levels of oxidative markers in the saliva of patients with periodontitis.

Introducción. La periodontitis afecta a más del 20 % de la población latinoamericana. La presencia de marcadores de estrés oxidativo se asocia con una mayor progresión de periodontitis, por lo que su rol en la patogenia debe estudiarse. Objetivo. Determinar la prevalencia de las principales bacterias y virus asociados con la periodontitis y estimar la capacidad antioxidante total y la peroxidación de lípidos en la saliva de los pacientes con periodontitis. Materiales y métodos. Se hizo un estudio transversal en 87 sujetos sanos diagnosticados con periodontitis (P) según los criterios de los Centers of Disease Control and Prevention y la American Academy of Periodontology y 14 sujetos sin enfermedad periodontal como grupo control (C). En las muestras subgingivales se identificaron los principales virus y bacterias mediante técnicas de PCR. Los niveles de capacidad antioxidante total y malon-di-aldehído (MDA) se establecieron mediante espectrofotometría en muestras de saliva no estimulada. Resultados. Las medias de profundidad del sondaje y del nivel de inserción clínico periodontal en pacientes con periodontitis fueron 5,6 ± 1,7 y 6,1 ± 3,1 mm, respectivamente. Los microorganismos más prevalentes fueron Aggregatibacter actinomycetemcomitans (32,5 %) y Porphyromonas gingivalis (18,6 %). Los pacientes de áreas rurales registraron un mayor porcentaje de A. actinomycetemcomitans (urbano: 17,9 % Vs. rural: 48,9 %; p=0,0018). La frecuencia de los genes EBV, HSV1 y 2, y HCMV fue de 2,3 %. En pacientes con periodontitis se evidenciaron mayores niveles de MDA (P: 2,1 ± 1,5; C: 0,46 ± 0,3 µmol/g proteína; p=0,0001) y capacidad antioxidante total (P: 0,32 ± 0,2; C: 0,15 ± 0,1 mM; p<0,0036). La presencia de bacterias periodontales patógenas no modificó los marcadores oxidativos. Conclusiones. Aggregatibacter actinomycetemcomitans fue el agente patógeno mas prevalente. Su presencia no modificó los niveles de marcadores oxidativos en la saliva de los pacientes con periodontitis.

Epstein-Barr virus-infected plasma cells in periodontitis lesions.

Growing evidence supports that the Epstein-Barr virus (EBV) is a putative periodontal pathogen, but little is known regarding EBV behavior in periodontitis. Here, EBV infection was monitored in saliva and periodontal pocket (PP), at baseline and 3 months after periodontal non-surgical therapy (p-NST) in 20 patients diagnosed with periodontitis. After the treatment, the patients with the improved periodontal condition (good responders) showed a significant decrease in salivary EBV load. In contrast, in poor responders, EBV load was slightly increased. Moreover, after the therapy, most patients showed clear signs of EBV infection in a deep PP (≥5 mm) selected as a study site. To investigate how EBV can persist in a PP, we further investigate cellular sites of viral replication in PP. We identified large amounts of infiltrated EBV-infected cells, mostly overlapping with CD138+ plasma cells (PC). EBV-infected PCs formed high-density clusters within the infiltrate and along the periodontal epithelium which were commonly associated with CD3+ T-cells and CD20+ B-cells to evoke diffuse ectopic lymphoid-like structures. Taking together, this study provides new insights to support a model where the periodontal condition may play a major role in oral EBV shedding. Since PC harbors the late productive phases of EBV replication, the periodontal condition may favor B-cell differentiation with possible amplification of periodontal EBV infection and viral spreading. PCs have long been recognized as pathogenic markers in inflammatory lesions. Our finding sheds new light on the role of EBV infection and PC in periodontitis.

Association between human cytomegalovirus and periodontitis: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Human cytomegalovirus (HCMV) has been associated with periodontitis and apical periodontitis. The objective of this systematic review was to evaluate the association between HCMV and periodontitis, and apical periodontitis of endodontic origin. MATERIAL AND METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines and registered in the International prospective register of systematic reviews (PROSPERO). The search for potential studies was performed in MEDLINE via PubMed, Scopus, and SciELO. A quality assessment of the studies, publication bias analysis, and meta-analysis was performed. The results are presented in odds ratio with 95% confidence interval with the corresponding Forest plot. Sensitivity analysis was performed to evaluate the consistency of the results. RESULTS: Thirty-two studies were included in the quantitative and qualitative analyses. Of these, 26 were in periodontitis patients and 6 in apical periodontitis patients. Forest plot of combined studies revealed significant increased odds for periodontitis when subgingival HCMV was detected (OR 5.31; 95% CI 3.15-8.97). Sensitivity analysis based on quality of the included studies, showed consistent results. In contrast, the odds ratio for apical periodontitis when HCMV was detected from apical lesions was not statistically significant (OR 3.65; 95% CI 0.49-27.10). CONCLUSIONS: The results from the meta-analysis indicate that HCMV is significantly associated with periodontitis. In contrast, HCMV infection is not associated with apical periodontitis.

Oral human cytomegalovirus prevalence and its relationships with periodontitis and Porphyromonas gingivalis in Japanese adults: a cross-sectional study

Abstract Objective This study aimed to clarify the association between oral human cytomegalovirus (HCMV) and periodontitis in Japanese adults. Methodology In total, 190 patients (75 men and 115 women; mean age, 70.2 years) who visited Hiroshima University Hospital between March 2018 and May 2020 were included. Oral rinse samples were taken to examine the presence of HCMV DNA using real-time polymerase chain reaction (PCR). P. gingivalis was detected by semi-quantitative PCR analysis. Results HCMV DNA was present in nine of 190 patients (4.7%). There were significant associations between HCMV presence and the presence of ≥4-mm-deep periodontal pockets with bleeding on probing (BOP) (P<0.01) and ≥6-mm-deep periodontal pockets with BOP (P=0.01). However, no significant relationship was observed between HCMV presence and periodontal epithelial surface area scores. Logistic regression analysis revealed that the presence of ≥4-mm-deep periodontal pockets with BOP was significantly associated with HCMV (odds ratio, 14.4; P=0.01). Propensity score matching was performed between patients presenting ≥4-mm-deep periodontal pockets with BOP (i.e., active periodontitis) and patients without ≥4-mm-deep periodontal pockets with BOP; 62 matched pairs were generated. Patients who had ≥4-mm-deep periodontal pockets with BOP showed a higher rate of HCMV presence (9.7%) than those who lacked ≥4-mm-deep periodontal pockets with BOP (0.0%). There was a significant relationship between HCMV presence and ≥4-mm-deep periodontal pockets with BOP (P=0.03). A significant relationship was found between HCMV/P. gingivalis DNA presence and ≥4-mm-deep periodontal pockets with BOP (P=0.03). Conclusions Coinfection of oral HCMV and P. gingivalis was significantly associated with active periodontitis. Moreover, interactions between oral HCMV and P. gingivalis may be related to the severity of periodontal disease.

Association between human T cell leukemia virus 1 (HTLV-1) infection and advanced periodontitis in relation to hematopoietic activity among elderly participants: a cross-sectional study.

BACKGROUND: We reported that human T cell leukemia virus 1 (HTLV-1) infection is positively associated with atherosclerosis. Recent evidence has revealed a close association of periodontitis with atherosclerosis, endothelial dysfunction, and disruption of the microcirculation. However, the association between HTLV-1 and advanced periodontitis has not been investigated to date. Since hematopoietic activity is closely linked to endothelial maintenance activity and is known to decline with age, we hypothesized that the state of hematopoietic activity influenced the association between HTLV-1 and advanced periodontitis in elderly participants. METHODS: A cross-sectional study was performed including 822 elderly participants aged 60-99 years who participated in a dental health check-up. Advanced periodontitis was defined as a periodontal pocket ≥ 6.0 mm. Participants were classified as having low or high hematopoietic activity according to the median values of reticulocytes. RESULTS: HTLV-1 infection was positively related to advanced periodontitis among participants with lower hematopoietic activity (lower reticulocyte count), but not among participants with higher hematopoietic activity (higher reticulocyte count). The adjusted odds ratio (95% confidence interval) considering potential confounding factors was 1.92 (1.05-3.49) for participants with a lower reticulocyte count and 0.69 (0.35-1.36) for participants with a higher reticulocyte count. CONCLUSIONS: Among elderly participants, the association between HTLV-1 infection and advanced periodontitis is influenced by hematopoietic activity. Since hematopoietic activity is associated with endothelial maintenance, these findings provide an efficient tool for clarifying the underlying mechanism of the progression of periodontitis among elderly participants.

Redondoviridae, a Family of Small, Circular DNA Viruses of the Human Oro-Respiratory Tract Associated with Periodontitis and Critical Illness.

The global virome is largely uncharacterized but is now being unveiled by metagenomic DNA sequencing. Exploring the human respiratory virome, in particular, can provide insights into oro-respiratory diseases. Here, we use metagenomics to identify a family of small circular DNA viruses-named Redondoviridae-associated with human diseases. We first identified two redondovirus genomes from bronchoalveolar lavage samples from human lung donors. We then queried thousands of metagenomic samples and recovered 17 additional complete redondovirus genomes. Detections were exclusively in human samples and mostly from respiratory tract and oro-pharyngeal sites, where Redondoviridae was the second most prevalent eukaryotic DNA virus family. Redondovirus sequences were associated with periodontal disease, and abundances decreased with treatment. Some critically ill patients in a medical intensive care unit were found to harbor high levels of redondoviruses in respiratory samples. These results suggest that redondoviruses colonize human oro-respiratory sites and can bloom in several human disorders.

Real time detection and quantification of Epstein Barr virus in different grades of oral gingivitis and periodontitis patients.

BACKGROUND: Periodontal diseases are of microbial etiology and are globally causing loss of teeth in adult population. Many severe oral diseases have been recently associated to Herpes viruses, of which Epstein Barr Virus (EBV) and human cytomegalovirus (HCMV) have been indicated in the etiology of periodontal diseases. AIM: The purpose of the study was to compare the effect of EBV in different types of periodontal diseases namely acute gingivitis, chronic gingivitis, acute and chronic, localized and generalized aggressive (juvenile) periodontitis and apical periodontitis. MATERIAL AND METHOD: 70 individuals were included in this study. Supragingival plaque and plaque from two deepest sites of the periodontal pockets were collected then stored at 70° c and prepared for nucleic acid extraction. For EBV detection, DNA were extracted from the plaque samples with the QIAamp DNA mini kit. Q-PCR was performed by targeting the non-polymorphic Epstein-Barr nuclear antigen-1 (EBNA-1) gene using Corbett Research 6000 Q-PCR instrument and Rotor gene 6000 software. RESULTS: Overall prevalence of EBV in the disease group was 60% (27/45 patients) as compared to only 8% (4/25 people) in the normal population. The mean copy number of EBV DNA was found to be significantly higher in periodontitis (2234 ± 1811.34) when compared to gingivitis (554 ± 537.64, p = .001) and normal patients (370 ± 161.03, p < .001). CONCLUSION: Here, we found that the prevalence of EBV as well as copy number of EBV was significantly higher in periodontitis patients as compared to gingivitis patients or normal population.