New Viral Facets in Oral Diseases: The EBV Paradox Tonoyan, Lilit; Vincent-Bugnas, Séverine; Olivieri, Charles-Vivien ...
International journal of molecular sciences,
11/2019, Volume:
20, Issue:
23
Journal Article
Peer reviewed
Open access
The oral cavity contributes to overall health, psychosocial well-being and quality of human life. Oral inflammatory diseases represent a major global health problem with significant social and ...economic impact. The development of effective therapies, therefore, requires deeper insights into the etiopathogenesis of oral diseases. Epstein-Barr virus (EBV) infection results in a life-long persistence of the virus in the host and has been associated with numerous oral inflammatory diseases including oral lichen planus (OLP), periodontal disease and Sjogren's syndrome (SS). There is considerable evidence that the EBV infection is a strong risk factor for the development and progression of these conditions, but is EBV a true pathogen? This long-standing EBV paradox yet needs to be solved. This review discusses novel viral aspects of the etiopathogenesis of non-tumorigenic diseases in the oral cavity, in particular, the contribution of EBV in OLP, periodontitis and SS, the tropism of EBV infection, the major players involved in the etiopathogenic mechanisms and emerging contribution of EBV-pathogenic bacteria bidirectional interaction. It also proposes the involvement of EBV-infected plasma cells in the development and progression of oral inflammatory diseases. A new direction for preventing and treating these conditions may focus on controlling pathogenic EBV with anti-herpetic drugs.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
(1) Background: Obstructive sleep apnea (OSA) affects approximately 1% to 5% of children. To date, the main pathophysiological factor is adenotonsillar tissue hypertrophy. As many respiratory viruses ...can persist in secondary lymphoepithelial organs after upper airway infection, the objective of this systematic review was to investigate the link between history of viral infections and the risk of pediatric OSA. (2) Methods: Corresponding references were searched electronically (PubMed MEDLINE, Cochrane Library and Scopus) until 21 November 2022. Prospective or retrospective cohorts, evaluating the children suffering from OSA with history of viral infections and comparing them with children with no history of viral infections written in English, were included. Four independent reviewers selected studies, extracted data, and evaluated the risk of bias using ROBINS-I. (3) Results: Of 1027 potentially eligible articles, four studies (one retrospective, two prospective cohorts and one case-control) were included. (4) Conclusions: Exposure to lower airway infections may precede the diagnosis of pediatric OSA suggesting that respiratory viruses may play a mechanical role in the development of pediatric OSA. Further research is required to improve our understanding of the role of viral infections. Registration: PROSPERO CRD awaiting.
Junctional epithelium (JE) provides the front-line defense against pathogens invading periodontium. The breakdown of the JE barrier is the hallmark of periodontitis. Recent studies have implicated ...the Epstein-Barr virus (EBV) as one of the etiopathogenetic factors of periodontitis. EBV exhibits tropism for two target cells
: B cells, where it primarily remains latent, and epithelial cells, where viral replication occurs.
Our knowledge of junctional epithelial cell (JEC) infection with EBV has been limited by the difficulty of generating cell cultures and the inability to infect JECs
readily.
To study EBV infection in JECs, we developed human JEC cultures derived from a periodontitis patient. Furthermore, we established a successful contact-free co-culture infection model between the EBV-donor B95-8 cell line and the EBV-permissive JEC culture. JECs and EBV infection of JECs were detected using immunofluorescent staining of cytokeratin 19 and EBNA1, respectively. In addition, EBV infection was confirmed by RT-qPCR for EBNA1, LMP1, and BZLF1 expression.
Our results suggest that the infection of JECs with EBV can occur in an
experimental model. These outcomes have the potential to enhance our understanding of EBV's involvement in periodontitis and advance periodontal research.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
An amplifying role for oral epithelial cells (ECs) in Epstein-Barr Virus (EBV) infection has been postulated to explain oral viral shedding. However, while lytic or latent EBV infections of ...oro/nasopharyngeal ECs are commonly detected under pathological conditions, detection of EBV-infected ECs in healthy conditions is very rare. In this study, a simple non-surgical tissue sampling procedure was used to investigate EBV infection in the periodontal epithelium that surrounds and attaches teeth to the gingiva. Surprisingly, we observed that the gingival ECs of the periodontium (pECs) are commonly infected with EBV and may serve as an important oral reservoir of latently EBV-infected cells. We also found that the basal level of epithelial EBV-infection is significantly increased in chronic periodontitis, a common inflammatory disease that undermines the integrity of tooth-supporting tissues. Moreover, the level of EBV infection was found to correlate with disease severity. In inflamed tissues, EBV-infected pECs appear to be prone to apoptosis and to produce larger amounts of CCL20, a pivotal inflammatory chemokine that controls tissue infiltration by immune cells. Our discovery that the periodontal epithelium is a major site of latent EBV infection sheds a new light on EBV persistence in healthy carriers and on the role of this ubiquitous virus in periodontitis. Moreover, the identification of this easily accessible site of latent infection may encourage new approaches to investigate and monitor other EBV-associated disorders.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The expansion of adipose progenitor cells (APCs) plays an important role in the regeneration of the adipose tissue in physiological and pathological situations. The major role of CD26-expressing APCs ...in the generation of adipocytes has recently been highlighted, revealing that the CD26 APC subtype displays features of multipotent stem cells, giving rise to CD54- and CD142-expressing preadipocytes. However, a relevant human in vitro model to explore the regulation of the APC subpopulation expansion in lean and obese adipose tissue microenvironments is still lacking. In this work, we describe a novel adipose tissue model, named ExAdEx, that can be obtained from cosmetic surgery wastes. ExAdEx products are adipose tissue units maintaining the characteristics and organization of adipose tissue as it presents in vivo. The model was viable and metabolically active for up to two months and could adopt a pathological-like phenotype. The results revealed that inflammatory and fibrotic microenvironments differentially regulated the expansion of the CD26 APC subpopulation and its CD54 and CD142 APC progenies. The approach used significantly improves the method of generating adipose tissue models, and ExAdEx constitutes a relevant model that could be used to identify pathways promoting the expansion of APCs in physiological and pathological microenvironments.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background: SARS-CoV-2 quickly spreads in the worldwide population, imposing social restrictions to control the infection, being the massive testing another essential strategy to break the chain of ...transmission.
Aim: To compare the performance of at-home self-collected samples - saliva and combined nasal-oropharyngeal swabs (NOP) - for SARS-CoV-2 detection in a telemedicine platform for COVID-19 surveillance.
Material and methods: We analyzed 201 patients who met the criteria of suspected COVID-19. NOP sampling was combined (nostrils and oropharynx) and saliva collected using a cotton pad device. Detection of SARS-COV-2 was performed by using the Altona RealStar® SARS-CoV-2 RT-PCR Kit 1.0.
Results: There was an overall significant agreement (κ coefficient value of 0.58) between saliva and NOP. Considering results in either sample, 70 patients positive for SARS-CoV-2 were identified, with 52/70 being positive in NOP and 55/70 in saliva. This corresponds to sensitivities of 74.2% (95% CI; 63.7% to 83.1%) for NOP and 78.6% (95% CI; 67.6% to 86.6%) for saliva.
Conclusion: Our data show the feasibility of using at-home self-collected samples (especially saliva), as an adequate alternative for SARS-CoV-2 detection. This new approach of testing can be useful to develop strategies for COVID-19 surveillance and for guiding public health decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Periodontitis, an inflammatory condition that affects the structures surrounding the tooth eventually leading to tooth loss, is one of the two biggest threats to oral health. Beyond oral health, it ...is associated with systemic diseases and even with cancer risk. Obviously, periodontitis represents a major global health problem with significant social and economic impact. Recently, a new paradigm was proposed in the etiopathogenesis of periodontitis involving a herpesviral-bacterial combination to promote long-term chronic inflammatory disease. Periodontitis as a risk factor for other systemic diseases can also be better explained based on viral-bacterial etiology. Significant efforts have brought numerous advances in revealing the links between periodontitis and Epstein-Barr virus (EBV), a gamma herpesvirus ubiquitous in the adult human population. The strong evidence from these studies may contribute to the advancement of periodontitis research and the ultimate control of the disease. Advancing the periodontitis research will require implementing suitable methods to establish EBV involvement in periodontitis. This review evaluates and summarizes the existing methods that allow the detection and diagnosis of EBV in periodontitis (also applicable in a more general way to other EBV-related diseases), and discusses the feasibility of the application of innovative emerging technologies.
The aim of this study was to test the application in vitro of different laser wavelengths at a low fluence in combination or not with proper photosensitizing dyes on Candida albicans biofilm with or ...without a synthetic killer decapeptide (KP).Candida albicans SC5314 was grown on Sabouraud dextrose agar plates at 37°C for 24 h. Cells were suspended in RPMI 1640 buffered with MOPS and cultured directly on the flat bottom of 96-wells plates. The previously described killer decapeptide KP was used in this study.Three different combinations of wavelengths and dyes were applied, laser irradiation has been performed at a fluence of 10 J/cm2. The effect on C. albicans biofilm was evaluated by the XTT assay. Microscopic observations were realized by fluorescence optic microscopy with calcofluor white and propidium iodide.Compared with control, no inhibition of C. albicans biofilm viability was obtained with application of red, blue and green lasers alone or with any combination of red diode laser, toluidine blue and KP. The combined application of blue diode laser with curcumin and/or KP showed always a very significant inhibition, as curcumin alone and the combination of curcumin and KP did, while combination of blue diode laser and KP gave a less significant inhibition, the same obtained with KP alone. The combined application of green diode laser with erythrosine and/or KP showed always a very significant inhibition, as the combination of erythrosine and KP did, but no difference was observed with respect to the treatment with erythrosine alone. Again, combination of green diode laser and KP gave a significant inhibition, although paradoxically lower than the one obtained with KP alone.Treatment with KP alone, while reducing biofilm viability did not cause C. albicans death in the adopted experimental conditions. On the contrary, combined treatment with blue laser, curcumin and KP, as well as green laser, erythrosine and KP led to death most C. albicans cells.The combination of laser light at a fluence of 10 J/cm2 and the appropriate photosensitizing agent, together with the use of KP, proved to exert differential effects on C. albicans biofilm.
The adenovirus VA1 RNA (VA1), a 160-nucleotide (nt)-long RNA transcribed by RNA polymerase III, is efficiently exported from
the nucleus to the cytoplasm of infected cells, where it antagonizes the ...interferon-induced antiviral defense system. We recently
reported that nuclear export of VA1 is mediated by a cis-acting RNA export motif, called minihelix, that comprises a double-stranded
stem (>14 nt) with a base-paired 5â² end and a 3â8-nt protruding 3â² end. RNA export mediated by the minihelix motif is Ran-dependent,
which indicates the involvement of a karyopherin-related factor (exportin) that remained to be determined. Here we show using
microinjection in Xenopus laevis oocytes that VA1 is transported to the cytoplasm by exportin-5, a nuclear transport factor for double-stranded RNA binding
proteins. Gel retardation assays revealed that exportin-5 directly interacts with VA1 RNA in a RanGTP-dependent manner. More
generally, in vivo and in vitro competition experiments using various VA1-derived, but also artificial and cellular, RNAs lead to the conclusion that exportin-5
preferentially recognizes and transports minihelix motif-containing RNAs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The acute phase of Crohn's disease (CD) is characterized by a large afflux of polymorphonuclear leukocytes (PMNL) into the mucosa and by the release of TNF-alpha. Conversion of inactive TNF-alpha ...into an active form requires the cleavage of a transmembrane TNF-alpha precursor by the TNF-alpha-converting enzyme (ADAM17), a protease mainly regulated by the tissue inhibitor of metalloproteinase 3 (TIMP3). The aim of the present study was to investigate in an in vitro model of PMNL transepithelial migration and in the intestinal mucosa of patients with CD the expression and regulation of ADAM17 and TIMP3 in intestinal epithelial cells (IEC). ADAM17 and TIMP3 expression was analyzed by Western blotting, RT-PCR, confocal microscopy, and immunohistochemistry by using the T84 model and digestive biopsies. ADAM17 expression in IEC was increased at a posttranscriptional level during the early phase (from 2 to 4 h) of PMNL transepithelial migration whereas TIMP3 was only increased 24 h later. TNF-alpha induced an early upregulation of ADAM17 in T84 cells, whereas PMNL adhesion, H(2)O(2), or epithelial tight junction opening alone did not affect the amount of ADAM17. Immunohistochemistry of intestinal biopsies revealed that strong expression of ADAM17 was associated with a high activity of CD. In contrast, TIMP3 was very poorly expressed in these biopsies. ADAM17 and TIMP3 profiling did not correlated with the NOD2/CARD15 status. The ADAM17 activity was higher both in the early phase of PMNL transepithelial migration and in active CD. These results showed early posttranscriptional upregulation of ADAM17 in IEC linked to PMNL transepithelial migration and a high activity of CD.
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