Virus en patología pulpar y periapical. Revisión de la literatura / Viruses in pulp and peri apical pathosis. Review

Introducción: Las infecciones de origen endodóncico son infecciones polimicrobianas que pueden tener diversas manifestaciones clínicas y radiológicas. La presencia de virus en diferentes patologías pulpares y periapicales está en investigación con el fin de asociar su presencia con las lesiones radiolúcidas apicales y sus sintomatología. El objetivo de este estudio es analizar la evidencia científica disponible en la actualidad que relaciona la presencia de virus en diferentes patologías de endodoncia y sus posibles implicaciones clínicas. Métodos: Se hace una revisión en la base de datos Medline/Publine, utilizando diferentes parámetros de búsqueda, seleccionando posteriormente los artículos más relevantes, que cumplieron con el criterio de búsqueda. De igual manera se hace una búsqueda en Scielo e IME. Resultados: Se incluyeron un total de 21 artículos, de los cuales 17 detectan la presencia del virus en una de las muestras. En tres de los estudios, la presencia viral no se encontró en ninguna de las muestras estudiadas. Los virus que se encontraron con mayor frecuencia fueron el virus de Epstein-Barr y citomegalovirus; sin embargo, en algunos de estos estudios han aparecido agentes virales como el herpes humano 6 y 8 virus. La relación entre presencia viral y sintomatología no es posible detectarla en todos los estudios, y lo mismo sucede con el tamaño de la lesión. Conclusión: Es necesario examinar y comprender la relación microbiológica que se establece en las patologías de origen endodóncico, dando lugar a nuevas opciones terapéuticas y de tratamiento

Introduction: Infections of an endodontic origin are polymicrobiobial infections that can have diverse clinical and radiographic manifestations. Recently, the presence of viruses in different endodontic pathologies is a focus of new research, associating their presence with symptomology and with apical radiolucent lesions. The goal of this study is to analyze the scientific evidence available currently that relates the presence of viruses in different endodontic pathologies and their possible clinical implications. Methods: A revision was carried out of the Medline/Publine database, using different search parameters, subsequently selecting the most relevant articles, which complied with the search criterion. Results: A total of 21 articles were included, and 17 detected the presence of viruses in one of the samples. In 3 of the studies, viral presence was not found in any of the sample studied. The viruses that were most frequently found were the Epstein-Barr and Cytomegaloviruses; however in some of these studies viral agents have appeared such as the human herpes 6 and 8 viruses. The relation between viral presence and symptomology is not possible to detect in all of the studies, which is the same for the relationship with large apical lesions. Conclusion: It is necessary to examine and understand the microbiological relationships that are established in pathologies of endodontic origin, leading to new therapeutic and treatment options

Significance of human cytomegalovirus and Epstein-Barr virus in inducing cytokine expression in periapical lesions.

INTRODUCTION: Because herpesviruses might be etiologically involved in periapical pathosis of endodontic origin, this study aimed to determine the occurrence of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), and the expression of mRNA transcripts of tumor necrosis factor (TNF)-α, γ-interferon (IFN), interleukin (IL)-1ß, IL-6, IL-12, and IL-10 in periapical granulomatous lesions collected in conjunction with apicoectomy. METHODS: A total of 9 symptomatic and 6 asymptomatic teeth with periapical lesions were studied. Periapical samples were collected in conjunction with apicoectomy, which was being performed because of radiographic evidence of incomplete periapical healing after conventional root canal therapy. By using established polymerase chain reaction primers and procedures, polymerase chain reaction assays were used to identify herpesvirus and cytokine gene expression. RESULTS: The difference in occurrence of HCMV, EBV, and cytokines between symptomatic and asymptomatic periapical lesions was statistically significant: HCMV (P = .048), EBV (P = .002), IFN (P = .001), IL-1 (P = .012), IL-6 (P = .026), IL-10 (P = .026), IL-12 (P = .012), and TNF (P < .001) (Mann-Whitney U test). There was a significant correlation between EBV, HCMV, and TNF, γ-IFN, IL-1, and IL-12 in symptomatic periapical lesions (Spearman test). CONCLUSIONS: The present findings provide evidence of a putative role of HCMV and EBV in the pathogenesis of symptomatic periapical pathosis. The release of tissue-destructive cytokines might be of pathogenetic significance.

Cytomegalovirus-infected inflammatory cells in dental periapical lesions.

INTRODUCTION: As cytomegalovirus may be etiologically involved in periapical pathosis of endodontic origin, this study aimed to determine the cellular source of periapical cytomegalovirus. METHODS: Periapical granulomatous tissue was collected from 15 extracted teeth with symptomatic periapical lesions. Multi-color flow cytometry was used to identify cytomegalovirus-infected cells. RESULTS: Cytomegalovirus infection was identified in 10 of the 15 (67%) study lesions, and in periapical monocytes/macrophages (40% of lesions) and T lymphocytes (54% of lesions), but not in periapical B lymphocytes. CONCLUSION: This study and previous polymerase chain reaction-based investigations show that cytomegalovirus is a frequent inhabitant of symptomatic periapical lesions.

Herpesviruses in abscesses and cellulitis of endodontic origin.

Acute apical abscesses and cellulitis are severe endodontic diseases caused by opportunistic bacteria with possible coinfection with latent herpesviruses. The objectives of this study are to identify herpesviruses, including human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), herpes simplex virus-1 (HSV-1), and Varicella zoster virus (VZV) in patients (n = 31) presenting with acute apical abscesses and cellulitis of endodontic origin. Primary and nested polymerase chain reaction (PCR) was conducted using virus-specific primers and DNA isolated from cell-free abscess fluid. From patients exhibiting concurrent spontaneous pain (n = 28), nine abscesses contained HCMV, two abscesses contained EBV, one abscess contained HSV-1, and no abscesses contained VZV. Control PCR using genomic or recombinant templates showed detection limits to a single genomic copy of HCMV, 100 genomic copies for EBV, and 1 to 10 copies for HSV-1 with no cross-amplification between herpesviral DNA targets. Nested PCR was required for detection of herpesviral DNA in the abscess specimens, indicating that these viruses were present in low copy number. Filtration of abscess specimens and virus transfer experiments using human fibroblastic MRC-5 cells confirmed the presence of HCMV particles in several abscess specimens. We conclude that herpesviruses are present but not required for the development of acute apical abscesses and cellulitis of endodontic origin.

Herpes zoster associated with tooth resorption and periapical lesions.

A 72-year-old woman presented with multiple periapical lesions and resorption of teeth in a single quadrant 17 years after an attack of herpes zoster (shingles) of the maxillary division of the trigeminal nerve. It is possible that cases of tooth resorption that were previously classified as idiopathic may have a viral aetiology and we suggest that these patients should be asked about a previous attack of shingles.

Human cytomegalovirus, Epstein-Barr virus and bone resorption-inducing cytokines in periapical lesions of deciduous teeth.

BACKGROUND: A connection of herpesvirus periapical infection with symptomatic and large-size periapical lesions has been recognized in adult patients, but no data exist about a possible involvement of herpesviruses in severe periapical pathosis in children. Herpesviruses have the potential to elicit potent bone resorption-inducing cytokines in mammalian cells. AIM: This study aimed to determine the occurrence of human cytomegalovirus and Epstein-Barr virus DNA, and mRNA transcripts of receptor activator of nuclear kappa B ligand (RANKL), osteoprotegerin, core binding factor alpha-1, colony stimulating factor-1, transforming growth factor-beta, and monocyte chemoattractant protein-1 in periapical symptomatic pathosis of deciduous teeth. MATERIAL AND METHODS: Twelve deciduous molar teeth from patients aged 2-8 years were extracted due to severe periapical infection, and granulomatous tissue adherent to the root tip of the extracted teeth was collected using a surgical knife. Non-diseased pulpal tissue, obtained from 12 teeth extracted for orthodontic reasons, served as negative control. Polymerase chain reaction assays were employed to identify herpesvirus DNA and cytokine gene expression, using established polymerase chain reaction primers and procedures. RESULTS: Seven (58%) of the periapical lesions yielded human cytomegalovirus and eight (67%) Epstein-Barr virus. Only one (8%) periapical lesion showed neither human cytomegalovirus nor Epstein-Barr virus. In healthy pulpal tissue, one (8%) specimen demonstrated human cytomegalovirus and another (8%) specimen revealed Epstein-Barr virus. Of the cytokines examined, RANKL expression showed significantly higher occurrence in periapical pathosis than in healthy pulpal tissue (P < 0.040). No relationship was identified between the type of herpesvirus and cytokine expression in the periapical lesions studied. CONCLUSIONS: The present findings provide evidence of a putative role of human cytomegalovirus and Epstein-Barr virus in the pathogenesis of symptomatic periapical pathosis in deciduous teeth. Increased RANKL expression in periapical lesions may be of pathogenetic significance.

Herpesviral-bacterial coinfection in periapical pathosis.

Two members of the herpesvirus family, human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), seem to be important putative pathogens of human periodontitis and symptomatic periapical lesions, causing pathosis either by inducing immunosuppression with a subsequent risk of aggressive bacterial infections or by infecting of periodontal cells directly. This study aimed to relate periapical occurrence of HCMV, EBV, and herpes simplex virus active infections to clinical characteristics of periapical lesions and periapical bacterial flora. Microbial samples were collected from 34 periapical lesions in conjunction with periapical surgery. Part of the periapical specimen was frozen for virologic examination, and another part was transferred to anaerobic transport medium for bacteriologic examination. RNA was isolated by means of a guanidinium isothiocyanate-acid phenol procedure, and cDNA was produced using herpesvirus-specific primers and reverse-transcription polymerase chain reaction amplification. Bacteriologic examination was performed according to established anaerobic culture methods. Of the 34 periapical lesions studied, 20 showed both HCMV and EBV, seven showed only HCMV, one showed only EBV, and six showed neither HCMV nor EBV. Herpes simplex virus was detected in two lesions. Higher occurrence of herpesvirus was detected in large versus small periapical lesions (p < 0.001) and in symptomatic versus asymptomatic periapical lesions (p < 0.001). A total of 18 microbial groups and an average of 2.1 to 3.0 bacterial groups were isolated from various categories of periapical lesions. The important finding of this study was that most teeth with necrotic pulp and periapical lesions harbored herpesviruses in periapical granulomatous tissue. Herpesvirus species in cooperation with endodontopathic bacteria may play major roles in the etiopathogenesis of aggressive types of periapical pathosis in humans.

Herpesviruses in periapical pathosis: an etiopathogenic relationship?

BACKGROUND: Much remains to be learned about the etiopathogenesis of periapical pathosis, especially about the molecular events preceding and causing disease onset. Human cytomegalovirus and Epstein-Barr virus, 2 herpesviruses, are discussed in this review as they relate to apical periodontitis in humans. RESULTS: Cytomegalovirus or Epstein-Barr virus active infections are detected in more than 90% of granulomas of symptomatic and large periapical lesions. Dual infection with cytomegalovirus and Epstein-Barr virus is closely associated with symptomatic lesions. Herpes simplex virus active infection has no apparent relationship to periapical disease. DISCUSSION: The available evidence suggests the involvement of active cytomegalovirus and Epstein-Barr infections in the etiopathogenesis of apical periodontitis. In periapical pathosis, herpesviruses may cause the release of tissue-destructive cytokines, the overgrowth of pathogenic bacteria, and the initiation of cytotoxic or immunopathologic events. Immune impairment resulting from herpesvirus infection may aid bacteria at several stages of the pathogenesis of periapical lesions, including growth in the periapical environment, possible invasion of tissue, and direct damage to tissue. Unraveling the etiology and pathogenesis of periapical pathosis may require a broadening of our experimental approaches to include studies on interactions among herpesviruses, bacteria, and host immune reactions. Understanding the significance of herpesviruses in the development of periapical lesions may aid in the diagnosis, prevention, and treatment of the diseases.

Cytomegalovirus and Epstein-Barr virus are associated with symptomatic periapical pathosis.

BACKGROUND: Recent studies have identified human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in symptomatic periapical lesions. Little information exists on HCMV and EBV in asymptomatic periapical lesions. AIM: To compare the presence of late transcripts of HCMV, EBV and herpes simplex virus (HSV) in symptomatic and asymptomatic periapical lesions. METHODS: Periapical samples were collected from seven symptomatic and seven asymptomatic periapical lesions at the time of apicoectomy. HCMV, EBV and HSV late mRNAs were identified by reverse transcription polymerase chain reaction. RESULTS: HCMV mRNA was detected in all seven symptomatic periapical lesions and in one asymptomatic lesion (Chi-squared test, Yates'P-value = 0.007). EBV mRNA was detected in six symptomatic lesions and in one asymptomatic lesion (P = 0.04). One asymptomatic lesion yielded HSV mRNA. CONCLUSIONS: HCMV and EBV active infections are associated with acute exacerbation of apical periodontitis. HSV seems to be unimportant in periapical pathosis.

Cytomegalovirus and Epstein-Barr virus DNA transcription in endodontic symptomatic lesions.

OBJECTIVES: Productive Herpesviridae infections are implicated in the etio-pathogenesis of aggressive periodontitis. However, virtually nothing is known about a possible role of herpesviruses in pulpal and periapical pathosis. This study employed a cDNA analysis to determine transcription of human cytomegalovirus (HCMV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV) in 14 recalcitrant periapical lesions and in 2 periapical healthy control sites. METHODS: Periapical samples were collected in conjunction with periapical surgery and kept frozen until virologic examination. RNA was isolated from periapical tissue by using a guanidinium isothiocyanate-acid phenol procedure (TRIZOL LS Reagent, GIBCO BRL, Rockville, MD). cDNAs were amplified by means of oligonucleotides targeting highly conserved regions of the test viruses and the RT-PCR-100 amplification kit (Sigma-Aldrich, St Louis, MO). Standardization of PCR primer sensitivity and validation was carried out according to established methods. Amplification products were identified by agarose gel electrophoresis. RESULTS: HCMV transcript was detected in 12 of 13 symptomatic and in 1 asymptomatic periapical lesion. EBV transcript was demonstrated in 8 of the 13 symptomatic lesions but not in the asymptomatic periapical lesion. HCMV and EBV dual transcription occurred at higher frequency in periapical lesions showing radiographic bone destruction of 5 mm x 7 mm or larger than in smaller size lesions (P = 0.03; Chi-squared test). No HCMV or EBV transcription was identified in the 2 healthy control sites. HSV transcript was not detected in any study site. CONCLUSION: The present data suggest that HCMV or EBV infections participate in the pathogenesis of periapical symptomatic lesions. Herpesviruses may produce periapical pathosis as a direct result of viral infection and replication, or as a consequence of virally induced impairment of the host defense and subsequent increased virulence of resident bacterial pathogens.