Online First 2025-08-28. Bibliogr.

Periodontitis (PD) is a chronic inflammatory disease of the periodontium with a high prevalence and is considered a potential risk factor for the development of other diseases. These include viral infections of the upper and lower respiratory tracts, including those caused by the Herpesviridae family, human immunodeficiency virus, hepatitis C and B viruses, influenza virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which have been identified with greater frequency in patients with PD. The underlying molecular mechanisms that underpin this comorbidity remain to be elucidated; however, the compromised capacity of the oral mucosa-associated antiviral response is a plausible explanation. Driven by clinical data that revealed the Herpesviridae family as the most commonly identified viruses in PD patients, this study was aimed to determine the effect of Porphyromonas gingivalis, the key etiological factor in periodontitis, on the development of herpes simplex virus-1 (HSV-1) infection. Using a model of the human gingiva, it was demonstrated that P. gingivalis significantly increases infection with HSV-1, promoting tissue distribution and propagation of the virus. This phenomenon can be attributed to the impairment of the interferon response, a consequence of proteolytic modifications of major signaling components catalyzed by Kgp gingipain. Furthermore, P. gingivalis infection has been observed to promote reactivation of HSV-1 in neuronal cells but via IFN-independent mechanism. These findings, demonstrating the attenuation of the host defense, expand our basic knowledge of the mechanisms underlying polymicrobial infections and clarify the observed comorbidity of PD with viral disorders.