Oral herpes is a highly prevalent infection caused by herpes simplex virus 1 (HSV-1). After an initial infection of the oral cavity, HSV-1 remains latent in sensory neurons of the trigeminal ganglia. Episodic reactivation of the virus leads to the formation of mucocutaneous lesions (cold sores), but asymptomatic reactivation accompanied by viral shedding is more frequent and allows virus spread to new hosts. HSV-1 DNA has been detected in many oral tissues. In particular, HSV-1 can be found in periodontal lesions and several studies associated its presence with more severe periodontitis pathologies. Since gingival fibroblasts may become exposed to salivary components in periodontitis lesions, we analyzed the effect of saliva on HSV-1 and -2 infection of these cells. We observed that human gingival fibroblasts can be infected by HSV-1. However, pre-treatment of these cells with saliva extracts from some but not all individuals led to an increased susceptibility to infection. Furthermore, the active saliva could expand HSV-1 tropism to cells that are normally resistant to infection due to the absence of HSV entry receptors. The active factor in saliva was partially purified and comprised high molecular weight complexes of glycoproteins that included secretory Immunoglobulin A. Interestingly, we observed a broad variation in the activity of saliva between donors suggesting that this activity is selectively present in the population. The active saliva factor, has not been isolated, but may lead to the identification of a relevant biomarker for susceptibility to oral herpes. The presence of a salivary factor that enhances HSV-1 infection may influence the risk of oral herpes and/or the severity of associated oral pathologies.
Zuo, Yi; Whitbeck, J Charles; Haila, Gabriel J; Hakim, Abraham A; Rothlauf, Paul W; Eisenberg, Roselyn J; Cohen, Gary H; and Krummenacher, Claude, "Saliva enhances infection of gingival fibroblasts by herpes simplex virus 1." (2019). Faculty Scholarship for the College of Science & Mathematics. 149.
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Zuo Y, Whitbeck JC, Haila GJ, Hakim AA, Rothlauf PW, Eisenberg RJ, Cohen GH, & Krummenacher C. Saliva enhances infection of gingival fibroblasts by herpes simplex virus 1. PLoS One. 2019 Oct 3;14(10):e0223299. doi: 10.1371/journal.pone.0223299. eCollection 2019. PubMed PMID: 31581238; PubMed Central PMCID: PMC6776388.