Periodontal herpesviruses: prevalence, pathogenicity, systemic risk.

Periodontitis is an infectious/inflammatory disease characterized by the loss of periodontal ligament and alveolar bone. Herpesviruses are frequent inhabitants of periodontitis lesions, and the periodontopathogenicity of these viruses is the topic of this review. In 26 recent studies from 15 countries, subgingival cytomegalovirus, Epstein-Barr virus and herpes simplex virus type 1, respectively, yielded median prevalences of 49%, 45% and 63% in aggressive periodontitis, 40%, 32% and 45% in chronic periodontitis, and 3%, 7% and 12% in healthy periodontium. An active herpesvirus infection of the periodontium exhibits site specificity, is a potent stimulant of cellular immunity, may cause upgrowth of periodontopathic bacteria and tends to be related to disease-active periodontitis. Pro-inflammatory cytokines induced by the herpesvirus infection may activate matrix metalloproteinases and osteoclasts, leading to breakdown of the tooth-supportive tissues. The notion that a co-infection of herpesviruses and specific bacteria causes periodontitis provides a plausible etiopathogenic explanation for the disease. Moreover, herpesvirus virions from periodontal sites may dislodge into saliva or enter the systemic circulation and cause diseases beyond the periodontium. Periodontal treatment can diminish significantly the periodontal load of herpesviruses, which may lower the incidence and magnitude of herpesvirus dissemination within and between individuals, and subsequently the risk of acquiring a variety of medical diseases. Novel and more effective approaches to the prevention and treatment of periodontitis and related diseases may depend on a better understanding of the herpesvirus-bacteria-immune response axis.

Failure to detect an association between aggressive periodontitis and the prevalence of herpesviruses.

BACKGROUND: Herpes simplex virus type 1 (HSV-1), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been suspected to play a causal role in periodontitis pathogenesis. The aim of this study was to determine the prevalence of these viruses in subgingival plaque samples of Caucasian patients with generalized aggressive periodontitis compared to periodontally healthy controls. METHODS: A total of 65 patients with aggressive periodontitis and 65 unmatched controls from Germany were investigated in the study. Subgingival plaque samples were analysed for the presence of HSV-1, EBV and HCMV by quantitative real-time polymerase chain reaction assays. Viral antibody titres were determined quantitatively by immunosorbent assays. RESULTS: DNA of HSV-1 and HCMV were detected in 1.5% of the patients and controls, whereas EBV DNA was present in 10.8% and 13.9% respectively. Detection rates of serum IgG against HSV-1 (76.1% versus 73.9%), EBV (98.5% versus 96.9%), HCMV (47.7% versus 46.2%) and IgM levels against HSV-1 (6.2% versus 1.5%), EBV (0% versus 0%), HCMV (0% versus 1.5%) did not significantly differ between patients and controls. CONCLUSION: The data of our study do not suggest any contribution of HSV-1, EBV or HCMV to aggressive periodontitis in a German population. Ethnic and methodological aspects might have caused conflicting results of previous studies.

Severe presentation of necrotizing ulcerative periodontitis in a Nigerian HIV-positive patient: a case report.

OBJECTIVE: To report a case of severe necrotizing ulcerative periodontitis (NUP) with a rarely associated sequestrum formation in a Nigerian HIV-positive patient. CLINICAL PRESENTATION AND INTERVENTION: A 47-year-old HIV-positive male patient with no history of previous dental visits presented with a severe toothache in his lower jaw of 4 weeks' duration, which had affected his ability to chew properly. Clinical examination revealed marked gingival inflammation, moderate gingival recession and mobility of some of his lower anterior teeth: 31, 32, and 33. There was also a sequestrum present associated with the affected teeth. His CD4 cell count was 226 cells/mm(3). His viral load was very high (360,082 copies/ml). The intervention included thorough debridement of the necrotic lesion and sequestrectomy. The patient responded well to treatment after 1 week of follow-up. Unfortunately, the CD4 count was not assessed further because the patient was lost to follow-up. CONCLUSION: This case showed that a high CD4 cell count does not necessarily prevent the occurrence of NUP in HIV-positive patients. Intervention might have enhanced a rapid positive response to the treatment within a short time.

Low prevalence of subgingival viruses in periodontitis patients.

BACKGROUND: Viruses such as Human Cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) have been proposed to be periodontal pathogens. The aim of this study was to analyse the presence of herpesvirus DNA in subgingival plaque samples of patients with different forms of periodontitis and in healthy periodontia. MATERIALS AND METHODS: A total of 140 ethnically mixed (prevalently Caucasian) subjects took part in the study. Sixteen were affected by localized aggressive periodontitis (LAgP), 64 by generalized aggressive periodontitis (GAgP), 20 by chronic periodontitis (CP) and 40 were periodontally healthy. Polymerase chain reaction (PCR) analyses were performed to detect HCMV and EBV. Sera were tested for anti-HCMV and EBV IgG antibodies. PCRs for herpes simplex (HSV) and varicella zoster virus (VZV) were performed in subgingival samples from a subset of 20 AgP subjects. RESULTS: HCMV DNA was not detected in any plaque samples. EBV DNA was detected in four LAgP (25%), two GAgP (3%) subjects and four healthy individuals (10%). HSV DNA and VZV DNA were not detected in the subset of studied individuals. CONCLUSIONS: This study challenges the previously reported high prevalence of herpesvirus DNA in subgingival samples from periodontitis patients and so questions whether they act as pathogens in such patients.

Herpesviruses in chronic and aggressive periodontitis patients in an Indian population.

Many recent studies have assessed the prevalence and role of herpesviruses in the etiopathogenesis of periodontal diseases, which has led to the realization of intricate interactions between viruses and bacteria within periodontal pockets. It has also been shown that the occurrence of herpesviruses may vary depending upon the age of the patient and the race of the population studied. Thus, the present study aimed at detecting herpes simplex virus type 1 and 2 (HSV 1 and 2), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in periodontal pockets of Indian patients with chronic and aggressive periodontitis. Subgingival plaque samples (n = 33) were collected from 19 randomly chosen chronic periodontitis and 14 aggressive periodontitis patients. Herpesviruses were detected using multiplex polymerase chain reaction technique. Chronic periodontitis patients revealed presence of HSV-1 in 19 (100%) samples, HSV-2 in 3 (15.7%), EBV in 15 (78.9%) and HCMV in 5 (26.31%) samples. Samples from aggressive periodontitis patients showed the presence of HSV-1 in 8 (57.14%), EBV in 4 (28.57%) and HCMV in 1 (7.14%), whereas HSV-2 was not detected in any specimen. In this population, herpesviruses were found more frequently in chronic periodontitis than in aggressive periodontitis patients and their prevalence may vary according to the age and race of the patient.

Gingival Recession and Localized Aggressive Periodontitis Among HIV-infected Children and Adolescents Receiving Antiretroviral Therapy.

BACKGROUND: Limited information is available on gingival recession or localized aggressive periodontitis among HIV-infected children and adolescents. This study reports on the prevalence of these conditions among children and adolescents receiving antiretroviral therapy (ART). METHODS: A cross-sectional study on HIV-infected children and adolescents attending a Pediatric HIV clinic in Gauteng, South Africa, between January 2013 and June 2016. Patients received an oral examination and oral hygiene instructions, irrespective of oral- or dental-related complaints. Hard and soft tissue pathology was managed and recorded, together with relevant demographic and clinical data. Statistical analysis was performed in Stata 14 with P < 0.05 as significant. RESULTS: A total of 554 children and adolescents 5-19 years of age (median age: 12.2 years; interquartile range: 10.3-14.9) were included, of whom 78 (14.1%) presented with gingival recession on permanent mandibular incisors and/or localized aggressive periodontitis of molar teeth. Multivariable logistic regression revealed that patients with gingival recession and aggressive periodontitis had a significantly shorter duration of ART and were more likely to have suboptimal HIV control (CD4 count ≤500 cells/µL and/or HIV viral load ≥50 copies/mL) and be on advanced ART regimens after virologic failure on first- and second-line treatment. CONCLUSIONS: The results emphasize the importance of oral health care among HIV-infected children and adolescents from the onset, to prevent and manage conditions that could result in tooth loss and permanent disfigurement. This is of particular importance in the presence of virologic failure and immunosuppression.

Human herpesvirus 7, Epstein-Barr virus and human cytomegalovirus in periodontal tissues of periodontally diseased and healthy subjects.

AIMS: To evaluate (i) the presence of human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV), and (ii) the transcription pattern of HHV-7 in gingival biopsies from patients affected by periodontitis (P) and periodontally healthy subjects (H). MATERIAL AND METHODS: Thirty-seven subjects (P: n=24; H: n=13) were included. Each P patient contributed two gingival biopsies (representative of a clinically affected and non-affected site) and each H subject contributed one gingival biopsy. After DNA extraction, nested polymerase chain reaction was used to identify the viruses. RESULTS: HHV-7 was detected in 91.7% of P patients and in 61.5% of H subjects (p=0.02), EBV in 50.0% samples of P patients and 7.7% of H subjects (p=0.005) and HCMV only in one sample from H group. EBV was more frequently detected in biopsies from affected sites (50.0%) than from non-affected sites (16.7%) (p=0.008). HHV-7 transcription was detected in 15.4% of affected and 15.4% of non-affected sites. CONCLUSIONS: The results indicate that (i) gingival tissues can be considered a potential reservoir for HHV-7; (ii) when present, HHV-7 persists in a latent state in the majority of cases; (iii) the presence of EBV seems to be associated with the diseased state of the patient and site.

Detection of herpesviruses and periodontal pathogens in subgingival plaque of patients with chronic periodontitis, generalized aggressive periodontitis, or gingivitis.

BACKGROUND: Herpesviruses may be related to the etiology of aggressive periodontitis (AgP) and chronic periodontitis (CP) by triggering periodontal destruction or by increasing the risk for bacterial infection. This case-control study evaluated the presence of herpes simplex virus type I (HSV-1), Epstein-Barr virus type I (EBV-1), human cytomegalovirus (HCMV), Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Prevotella intermedia, and Tannerella forsythia (previously T. forsythensis) in patients with generalized AgP (AgP group), CP (CP group), or gingivitis (G group) and in healthy individuals (C group). METHODS: Subgingival plaque samples were collected with paper points from 30 patients in each group. The nested polymerase chain reaction (PCR) method was used to detect HSV-1, EBV-1, and HCMV. Bacteria were identified by 16S rRNA-based PCR. RESULTS: HSV-1, HCMV, and EBV-1 were detected in 86.7%, 46.7%, and 33.3% of the AgP group, respectively; in 40.0%, 50.0%, and 46.7% of the CP group, respectively; in 53.3%, 40.0%, and 20.0% of the G group, respectively; and in 20.0%, 56.7%, and 0.0% of the C group, respectively. A. actinomycetemcomitans was detected significantly more often in the AgP group compared to the other groups (P <0.005). P. gingivalis and T. forsythia were identified more frequently in AgP and CP groups, and AgP, CP, and G groups had higher frequencies of P. intermedia compared to the C group. CONCLUSION: In Brazilian patients, HSV-1 and EBV-1, rather than HCMV, were more frequently associated with CP and AgP.

[Relationship between herpesviruses and periodontal pathogenic bacteria in subgingival plaque].

OBJECTIVE: To evaluate the prevalence rates of human cytomegalovirus(HCMV) and Epstein-Barr virus-1(EBV-1) in subgingival plaque and analyze the relationship between herpesviruses, periodontal pathogenic bacteria and periodontal clinical parameters in Chinese patients with aggressive periodontitis(AgP). METHODS: A total of one hundred and twenty subgingival plaque samples were collected from 89 AgP patients and 31 healthy subjects. HCMV and EBV-1 were detected using nested polymerase chain reaction(PCR).Contemporaneously, 8 periodontal pathogenic bacteria including Actinobacillus actinomycetemcomitans(Aa), Porphyromonas gingivalis(Pg), Tannerella forsythensis(Tf), Prevotella intermedia(Pi), Campylobacter rectus(Cr),Fusobacterium nucleatum(Fn), Treponema denticola(Td), Prevotella nigrescens(Pn) were detected by 16S rRNA based PCR. RESULTS: HCMV was more frequently detected in AgP patients (43.8%) than in healthy controls (12.9%, P<0.01). The prevalence rates of HCMV and EBV-1 in AgP patients with 6-8 kinds of bacteria detected were 54.4% and 17.4%, respectively, significantly higher than those with 3-5 kinds of bacteria detected (P<0.05). CONCLUSION: The prevalence rates of HCMV and EBV was higher in AgP patients than in healthy controls. Herpesviruses and periodontal pathogenic bacteria may cooperate synergistically in the development of AgP, which could be considered as a pathogenetic consortium in future investigation of periodontaltitis.

Herpesviruses in etiopathogenesis of aggressive periodontitis: A meta-analysis based on case-control studies.

OBJECTIVE: Previous studies have found that herpesviruses are associated with aggressive periodontitis (AgP). However, these findings are controversial. This meta-analysis was aimed at clarifying the association between herpesviruses and AgP. METHODS: We identified eligible case-control studies evaluating the association between herpesviruses and AgP from PubMed and Embase databases in October 2015. Original data were extracted and quality assessment was done. Overall odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. Random-effects model was determined. The stability was evaluated by sensitivity analysis. Finally, Egger's funnel plot was used to investigate the publication bias. RESULTS: Twelve case-control studies involving 322 patients and 342 controls were included in the present meta-analysis. The included case-control studies were assessed as high quality. The quantitative synthesis results for Epstein-Barr virus (EBV) showed significance (10 studies: p = 0.0008, OR = 6.11, 95% CI = 2.13-17.51); nevertheless, evidence of publication bias for EBV was considerable (EBV: Egger's test, p<0.001). Human cytomegalovirus (HCMV) and Herpes simplex virus type 1 (HSV-1) had significant association with AgP (12 studies for HCMV: p = 0.009, OR = 3.63, 95% CI = 2.15-6.13; 4 studies for HSV-1: p<0.001, OR = 19.19, 95% CI = 4.16-79.06). Sensitivity analyses showed the results yielded consistency, and no significant publication bias was observed for HCMV. The association between Herpes simplex virus type 2 (HSV-2) and AgP was inconclusive (2 studies: p = 0.20, OR = 3.46, 95% CI = 0.51-23.51). CONCLUSION: This meta-analysis suggests that HCMV and HSV-1 are significantly associated with AgP. However, due to the heterogeneity among studies these conclusions should be cautiously interpreted. There is insufficient evidence to draw any conclusion between EBV, HSV-2 and AgP based on the currently limited data.

A 17-year old patient with DOCK8 deficiency, severe oral HSV-1 and aggressive periodontitis - a case of virally induced periodontitis?

We present a 17-year old girl with DOCK-8 deficiency, severe untreated oral HSV-1 infection and associated aggressive periodontitis. DOCK-8 deficiency is a primary immunodeficiency, caused by biallelicloss-of-function mutations in the DOCK8 gene, often leading to severe viral and fungal mucocutaneous infections. Nevertheless, to date DOCK8 has not been associated with severe periodontitis and inflammatory bone loss around teeth. Understanding whether DOCK8 deficiency or severe HSV-1 infection underlies susceptibility to periodontitis is central to this case and may provide insights into susceptibility factors for periodontitis in the general population. Our clinical and microbiological data suggest that severe HSV-1 infection is the driver of periodontal inflammation in this case.

Human herpesviruses and Porphyromonas gingivalis are associated with juvenile periodontitis.

BACKGROUND: Although herpesviruses have been associated with adult periodontitis, their relationship with juvenile periodontitis (JP) has not been established. This case-control study examined possible associations between JP and pathogenic bacteria, the human cytomegalovirus (HCMV), and the Epstein-Barr type 1 virus (EBV-1). METHODS: Subjects were participants in a larger survey of schoolchildren in North-Central Jamaica. Subgingival plaque samples from 15 subjects with JP, 20 with incipient periodontitis (IP), and 65 randomly-selected healthy controls were assayed for Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans using a 16S rRNA polymerase chain reaction (PCR) identification method, and for HCMV and EBV-1 using nested PCR identification. RESULTS: Strong bivariate associations were found between JP and P. gingivalis (odds ratio [OR] = 12.7; 95% CI = 2.6, 61.4), HCMV (OR = 10.0; 95% CI = 2.7, 36.3), and A. actinomycetemcomitans (OR = 8.0; 95% CI = 2.3, 27.5), but not EBV-1. In multivariate analyses, P. gingivalis remained a significant explanatory variable (OR = 7.8; 95% CI = 1.5, 40.9); however, the associations were marginal for HCMV (OR = 4.6; 95% CI = 0.9, 22.7), and non-significant for A. actinomycetemcomitans (OR = 2.0; 95% CI = 0.4, 9.7). The associations with JP and the extent of attachment loss were even stronger when both P. gingivalis and HCMV were detected together. P. gingivalis (OR = 3.9; 95% CI = 1.3, 12.0) and EBV-1 (OR = 3.3; 95% CI = 1.0, 10.3) were the only significant explanatory variables in the multivariate analysis of IP. CONCLUSIONS: P. gingivalis is the strongest and most stable indicator of periodontitis in Jamaican adolescents. Co-infection with P. gingivalis and HCMV appears to be particularly deleterious to periodontal health.

Host defensive, immunological, and microbiological observations of an early-onset periodontitis patient with virus-associated hemophagocytic syndrome.

Virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses: 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels (IL-1 beta, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.

Comparative analysis of presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1) in cases of chronic periodontitis and aggressive periodontitis with controls.

AIM: The aim of the present study was to evaluate the presence of Cytomegalovirus (CMV) and Epsteinbarr virus -1 (EBV-1)viruses in sub gingival plaque of chronic periodontitis (groupA), aggressive periodontitis patients (group B), periodontally healthy controls (group C) and to compare the clinical parameters between virus negative and positive sites in each of these groups. MATERIALS AND METHODS: Sixty subjects were included in the study and equally divided into the 3 groups (group A - 20, group B - 20, group C - 20). Sub gingival plaque samples were obtained from the 3 deepest periodontal pocket sites in case of subjects suffering from periodontitis, and from one random bleeding site per quadrant in healthy groups. Clinical parameters like plaque index (PI), gingival index (GI), pocket depth (PD) and clinical loss of attachment (CAL) were recorded. Viral Deoxyribonucleic acid (DNA) was extracted using Proteinase-K DNA Extraction method, and the presence of CMV and EBV-1 was detected by polymerase chain reaction and 2% agarose gel. RESULTS: Results of our study showed a 45% prevalence of CMV and EBV-1 in Aggressive periodontitis cases. Prevalence of CMV in chronic periodontitis and healthy subjects was 20% and 10%, respectively; while for EBV-1 it was 25% and 0%, respectively. In terms of comparison of the clinical parameters with virus presence, both CMV and EBV-1 positive sites showed a significantly higher mean pocket depth compared to virus negative sites. CONCLUSION: Our studyshowed that the prevalence of EBV1 was higher in chronic and aggressive periodontitis subjects compared to controls and the prevalence of CMV was higher in aggressive periodontitis patients. The virus positive sites showed higher pocket depth compared to virus negative sites.

Long-term stable periodontal regeneration by means of autologous bone grafting in patients with severe periodontitis.

Periodontal regeneration in patients with advanced periodontitis and severe attachment loss has classically presented some of the greatest challenges to the practitioner. The purpose of this article is to describe the staged treatment approach and long-term follow-up of a case with generalized advanced chronic periodontitis. Microbial sampling for suspected periodontopathogens was done before and after treatment. Autogenous bone grafting was used to repair bilateral mandibular vertical defects on both molars and premolars. Reentry surgery at 6 months demonstrated 100% defect fill. Clinical, radiographic, and microbiologic evidence at 8 years suggested a stable outcome. Qualitative polymerase chain reaction (PCR) analysis was done to detect the presence of cytomegalovirus, Epstein-Barr virus type 1, and common periodontopathogens 8 years after active periodontal therapy. Negative PCR results 8 years after treatment confirmed that pathogenic subgingival reservoirs were successfully eradicated.

Herpesvirus in localized juvenile periodontitis.

Herpesvirus genomic sequences can be detected in gingival crevicular fluid of adult periodontitis lesions. Herpesviruses are immunosuppressive and may facilitate establishment of subgingival pathogens. Electron microscopic studies have identified nuclear and cytoplasmic virus-like inclusions in gingival inflammatory cells from localized juvenile periodontitis (LJP). The present study aimed to determine if herpesviruses occur in LJP lesions and if human cytomegalovirus (HCMV) activation is associated with elevated levels of subgingival Actinobacillus actinomycetemcomitans, the putative bacterial pathogen of LJP. Eleven systemically healthy patients exhibiting LJP (10-23 yr) were studied. In each patient, subgingival samples were pooled from 3 periodontitis lesions around first molar and incisor teeth (5-11 mm periodontal pocket depth) and from 3 gingivitis/healthy sites around canines (2-3 mm periodontal pocket depth). Polymerase chain reaction (PCR) was used to detect herpesvirus DNA and HCMV cDNA of major capsid protein transcripts, indicative of viral activation. Selective culture and 16S rRNA PCR were used to identify A. actinomycetemcomitans. Of 11 deep periodontal samples, 8 showed HCMV, 7 showed Epstein-Barr virus type 1 (EBV-1), 1 showed EBV type 2, 6 showed herpes simplex virus (HSV) and 8 showed viral co-infection. Of 11 shallow periodontal samples, 2 showed HCMV, 2 showed EBV-1, 1 showed HSV and 2 showed viral co-infection. The difference in occurrence of HCMV and viral co-infection between deep and shallow periodontal sites was statistically significant (p =0.031). HCMV activation was detected in deep pockets of all 5 virally positive patients with early LJP (aged 10-14 years) but only in 1 of 3 virally positive LJP patients older than 14 years, and not in any shallow pocket tested. HCMV activation appeared related to absence of radiographic crestal alveolar lamina dura, a possible indication of periodontal disease progression. A. actinomycetemcomitans tended to be more prevalent in samples showing active than latent HCMV infection. The present findings are consistent with the notion that periodontal herpesvirus infection and possibly HCMV activation constitute important features of the etiopathogenesis of LJP.

Herpesviruses: a unifying causative factor in periodontitis?

Human cytomegalovirus and Epstein-Barr virus type 1 are discussed in this review as they relate to destructive periodontal disease in humans. Genomes of the two herpesviruses occur frequently in severe adult periodontitis, localized and generalized juvenile periodontitis, Papillon-Lefèvre syndrome periodontitis, Down's syndrome periodontitis, HIV-associated periodontitis and acute necrotizing ulcerative gingivitis. Herpesvirus infections generally involve a mild or asymptomatic primary phase followed by an asymptomatic latent phase interrupted sporadically by periods of activation, where viral replication and possibly clinical disease become manifest. Herpesvirus reactivation is triggered by a number of immunosuppressing factors, some of which have also been shown to be risk indicators of periodontal disease. Available evidence argues for the involvement of active cytomegalovirus infection in the initiation and progression of localized juvenile periodontitis and possibly other types of periodontal disease. In periodontal disease, herpesviruses may cause release of tissue-destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathogenic events. Understanding the significance of herpesviruses in the causation and pathogenesis of destructive periodontal diseases may have important implications in future prevention and treatment of the diseases.

Active cytomegalovirus infection in human periodontitis.

This study used the reverse transcription polymerase chain reaction method to determine mRNA transcription of subgingival human cytomegalovirus (HCMV) in six adult and three localized juvenile periodontitis patients. The oligonucleotide primers targeted the major capsid protein gene to determine active HCMV infection. HCMV major capsid protein transcript was detected in deep periodontal pockets of two adult and two localized juvenile periodontitis patients but not in any shallow periodontal sites. The findings suggest that active HCMV replication can occur in periodontal sites. Further studies are necessary to establish whether periodontal reactivation of HCMV correlates with the initiation or progression of destructive periodontal disease.