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.

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.

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.

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.

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.

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.

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.

Detection of a new species of torque teno mini virus from the gingival epithelium of patients with periodontitis.

We describe a novel species of torque teno mini virus called TTMV-204, which was isolated from the gingival epithelium of patients with periodontitis and characterized using viral metagenomics. The sequence of the full genome is 2824 nt in length. Phylogenetic analysis and genetic analyses show classic Betatorquevirus species organization with less than 40% amino acid similarity in ORF1. The prevalence of TTMV-204 in the periodontitis patient population was 18.75% (15/80), which was higher than in periodontally healthy individuals (10.00%, 10/80). However, the difference of the TTMV-204 prevalence between two groups was not statistically significant (p = 0.115). Further investigation is required to determine whether this new virus is associated with inflammation.

Porphyromonas gingivalis B cell Antigen Epitope Vaccine, pIRES-ragB'-mGITRL, Promoted RagB-Specific Antibody Production and Tfh Cells Expansion.

The outer membrane protein RagB is one of the major virulence factors of Porphyromonas gingivalis (P. gingivalis). To prevent periodontitis and associated systemic diseases induced by P. gingivalis, we built B cell antigen epitope vaccine characterized by pIRES-ragB'-mGITRL to induce a protective immune responses. The B cell antigen epitope and scrambled peptide of ragB were predicted, cloned into pIRES and constructed pIRES-ragB', pIRES-scrambled epitopes and pIRES-ragB'-mGITRL. pIRES-ragB'-mGITRL was transfected into COS-7 cells. Subsequently, the 6-week-old female BALB/c mice were challenged by P. gingivalis following three time immunization by pIRES, pIRES-ragB', pIRES-scrambled epitopes and pIRES-ragB'-mGITRL. The levels of RagB-specific antibody in the serum and Tfh cells in the spleen were measured by ELISA and flow cytometry, respectively. And higher levels of RagB-specific IgG were produced in the immunized mice with pIRES-ragB'-mGITRL. Additionally, the number of Tfh cells was also expanded and lesions were diminished in pIRES-ragB'-mGITRL mice comparing with control groups. Our results clearly demonstrated that P. gingivalis B cell antigen epitope vaccine, pIRES-ragB'-mGITRL, could induce protective immune responses. Furthermore, our data also indicated that pIRES-ragB'-mGITRL was a potential therapeutic vaccine against P. gingivalis.

Java project on periodontal diseases: periodontal bone loss in relation to environmental and systemic conditions.

OBJECTIVE: To assess in a population deprived from regular dental care the relationship between alveolar bone loss (ABL) and environmental/systemic conditions. MATERIAL & METHODS: The study population consisted of subjects from the Purbasari tea estate on West Java, Indonesia. A full set of dental radiographs was obtained of each subject and amount of ABL was assessed. In addition, the following parameters were evaluated: plasma vitamin C, vitamin D3 , HbA1c and CRP, the haptoglobin phenotype, presence of putative periodontopathic bacteria and viruses, dietary habits, smoking and anthropometrics. RESULTS: In this population 45% showed vitamin C depletion/deficiency, 82% had vitamin D3 insufficiency/deficiency, 70% were in a pre-diabetic state, 6% had untreated diabetes, 21% had elevated CRP values ranging from 3.1 to 16.1 mg/l. Results of the regression analysis, including all above mentioned parameters, showed four significant predictors, explaining 19.8% of the variance of ABL. Number of Porphyromonas gingivalis cells and CRP values showed a positive relationship with ABL, whereas BMI and number of guava fruit servings were negatively related. CONCLUSION: Results confirm previous findings that elevated levels of P. gingivalis may be indicative for periodontitis progression. A new finding is that guava fruit consumption may play a protective role in periodontitis in a malnourished population.

Biology and pathogenesis of cytomegalovirus in periodontal disease.

Human periodontitis is associated with a wide range of bacteria and viruses and with complex innate and adaptive immune responses. Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, Treponema denticola, cytomegalovirus and other herpesviruses are major suspected pathogens of periodontitis, and a combined herpesvirus-bacterial periodontal infection can potentially explain major clinical features of the disease. Cytomegalovirus infects periodontal macrophages and T-cells and elicits a release of interleukin-1ß and tumor necrosis factor-α. These proinflammatory cytokines play an important role in the host defense against the virus, but they also have the potential to induce alveolar bone resorption and loss of periodontal ligament. Gingival fibroblasts infected with cytomegalovirus also exhibit diminished collagen production and release of an increased level of matrix metalloproteinases. This article reviews innate and adaptive immunity to cytomegalovirus and suggests that immune responses towards cytomegalovirus can play roles in controlling, as well as in exacerbating, destructive periodontal disease.

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.

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.

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.

TLR3 agonist enhances CC chemokine ligand 20 production in IL-1ß-stimulated human gingival fibroblasts.

Viruses are related to the etiology of periodontitis. However, the role of viruses on Th17 cells infiltration in periodontitis lesions is unknown. Therefore, we examined the effects of TLR3 ligand on CCL20, which is related to Th17 cells migration, production in human gingival fibroblasts (HGFs). Polyinosinic-polycytidylic acid (Poly I:C), which is a TLR3 agonist, stimulation could moderately induce CCL20 production in HGFs. Poly I:C synergistically enhanced CCL20 expression from IL-1ß-stimulated HGFs. Inhibitors of p38 MAPK, extracellular signal-regulated kinase (ERK), c-Jun N terminal kinase (JNK), and NF-κB significantly inhibited CCL20 production in Poly I:C/IL-1ß-stimulated HGFs. Western blot analysis disclosed phosphorylation of p38 MAPK, JNK, and IκB-α were enhanced in Poly I:C/IL-1ß-treated HGFs. These data suggested that virus infection is related to Th17 cells migration in periodontitis lesion to induce CCL20 production in HGFs via TLR3. Therefore, our results indicated that virus might be important pathogen in periodontal disease.

Polybacterial challenge enhances HIV reactivation in latently infected macrophages and dendritic cells.

A polymicrobial infection comprising subgingival biofilms is the trigger for the chronic immunoinflammatory lesions of periodontitis. These microbial biofilms interface with host immune cells that increase with progressing disease and could result in HIV reactivation in HIV-1-infected patients. Previous reports have focused on the ability of monospecies challenge of macrophages and dendritic cells to detail molecular aspects of their detection and signalling pathways. This study provides a seminal description of the responses of macrophages and dendritic cells to a polybacterial challenge using various oral bacteria as prototype stimuli to examine these response characteristics. The investigation employed a model of HIV-promoter activation and reactivation of HIV viral replication. Oral Gram-negative bacteria elicited significantly greater levels of HIV promoter activation and viral replication from all cell types, compared with Gram-positive bacteria. Selected combinations of oral Gram-negative bacteria elicited synergistic HIV promoter activation and viral replication in macrophages and immature dendritic cells. In mature dendritic cells, there was no synergism in HIV promoter activation and viral replication. Gram-positive bacteria showed no synergism in any cell model. These findings support the importance of determining the characteristics and impact of polybacterial challenges on immune cells to clarify the potential immune recognition and antigen processing that can occur in the oral cavity.

Reactivation of latent HIV-1 infection by the periodontopathic bacterium Porphyromonas gingivalis involves histone modification.

Latently infected cells harbor the HIV-1 proviral DNA genome primarily integrated into heterochromatin, allowing the persistence of transcriptionally silent proviruses. Hypoacetylation of histone proteins by histone deacetylases (HDAC) is involved in the maintenance of HIV-1 latency by repressing viral transcription. In addition, periodontal diseases, caused by polymicrobial subgingival bacteria including Porphyromonas gingivalis, are among the most prevalent infections of mankind. Here we demonstrate the effects of P. gingivalis on HIV-1 replication. This activity could be ascribable to the bacterial culture supernatant but not to other bacterial components such as fimbriae or LPS. We found that this HIV-1-inducing activity was recovered in the lower molecular mass (<3 kDa) fraction of the culture supernatant. We also demonstrated that P. gingivalis produces high concentrations of butyric acid, acting as a potent inhibitor of HDACs and causing histone acetylation. Chromatin immunoprecipitation assays revealed that the corepressor complex containing HDAC1 and AP-4 was dissociated from the HIV-1 long terminal repeat promoter upon stimulation with bacterial culture supernatant concomitantly with the association of acetylated histone and RNA polymerase II. We thus found that P. gingivalis could induce HIV-1 reactivation via chromatin modification and that butyric acid, one of the bacterial metabolites, is responsible for this effect. These results suggest that periodontal diseases could act as a risk factor for HIV-1 reactivation in infected individuals and might contribute to the systemic dissemination of the virus.

[Detection of human papillomavirus in gingival fluid of Venezuelan HIV patients with periodontal disease]. / Detección de virus papiloma humano en el fluido gingival de pacientes con inmunodeficiencia humana y enfermedad periodontal.

Evidence suggests that viruses may be involved in the activation of periodontal disease, allowing the overgrowth of periodontal pathogens. The purpose of the present study was to detect the presence of Human Papillomavirus (HPV) in gingival crevicular fluid (GCF) in HIV+ Venezuelan patients with periodontal disease. We evaluated GCF samples from 20 HIV+ patients with periodontal disease from the Infectious Disease Center, Faculty of Dentistry, Central University of Venezuela, and were clinically examined to establish their periodontal conditions, 13 under HAART (antiretroviral therapy) and 7 without HAART. Seven seronegative patients with chronic periodontitis and 7 seronegative patients, without periodontal disease were included. DNA extraction was performed, the consensus primers MY09 and MY11 for the HPV L1 region were used for PCR amplification. Genotipification was made for the 6, 11, 16, 18, 31 and 45 genotypes. HPV were detected in 46% of HIV+ patients under therapy. The CD4 cell counts in the IIPV+ patients were not significantly different from the HPV-group. The viral load in the HPV+ group was significantly higher (200,470 +/- 324,244 copy/mL) than in the HPV-patients (10,246 +/- 23,805 copy/mL). Genotypes 6 and 11 were observed in the HPV positive samples, of which 4/6 (66.6%) presented coinfection with both types. No significant differences in the periodontal conditions were observed between patients with IIPV-HIV infection related to patients with only HIV. HPV was detected only in the gingival crevicular fluid of HIV+ patients under HAART independently of the periodontal conditions.