Herpes Simplex Virus Type 1 Infection of Human Periodontal Ligament

• Published in: International journal of molecular sciences Vol. 25; no. 15; p. 8466
• Main Authors: Ortis, Morgane, Chevalier, Marlène, Olivieri, Charles-Vivien, Vitale, Sébastien, Paul, Adrien, Tonoyan, Lilit, Doglio, Alain, Marsault, Robert
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.08.2024
• Subjects: Caspofungin; Cells; Cells, Cultured; Cytokines; Cytokines - metabolism; Epstein-Barr virus; Ethical aspects; Fibroblasts; Gene expression; Gum disease; Health aspects; Herpes simplex; Herpes Simplex - virology; Herpes simplex virus; Herpes viruses; Herpesvirus 1, Human - pathogenicity; Herpesvirus 1, Human - physiology; HSV-1; Humans; immune response; Infection; Infections; Interferon; Ligaments; Medical research; Medicine, Experimental; Morphology; oral diseases; Pathogenesis; periodontal inflammation; periodontal ligament; Periodontal Ligament - virology; Periodontium; Stem cells; viral infection; Viral infections; France; periodontal ligament; HSV-1; oral diseases; periodontal inflammation; viral infection; immune response
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25158466

The periodontal ligament (PDL) is a complex connective tissue that connects the tooth root to the dental alveolar bone and plays crucial mechanical roles. PDL also exhibits regenerative roles and regulatory functions to maintain periodontium integrity and homeostasis. While PDL exposure to oral microbial pathogens is common, virtually nothing is known regarding viral infections of PDL. In particular, human herpes simplex virus type 1 (HSV-1) persistently infects the oral cavity through infections of the oral epithelium, connective tissue and neurons. While the oral spread of HSV-1 is generally asymptomatic, this virus has also been implicated in various oral pathologies. In this study, using a primary cell model derived from PDL (PDL cells), and whole surgical fragments of PDL, we provide evidence supporting the efficient infection of PDL by HSV-1 and the promotion of cytopathic effects. Infection of PDL by HSV-1 was also associated with an acute innate inflammatory response, as illustrated by the production of antiviral interferons and pro-inflammatory cytokines. Furthermore, this inflammatory response to HSV-1 was exacerbated in the presence of bacterial-derived products, such as peptidoglycans. This work therefore highlights the ability of HSV-1 to infect mesenchymal cells from PDL, suggesting that PDL may serve as a viral reservoir for the periodontal spread of HSV-1. Moreover, this raises questions about HSV-1 oral pathogenesis, as HSV-1-associated cytopathic and inflammatory effects may contribute to profound alterations of PDL integrity and functioning.