Inflammatory Cytokine Changes in Herpes Simplex Virus Infected Periodontium: An In Vitro Proteomic Study.

OBJECTIVE

Periodontitis is the primary cause of tooth loss worldwide. This study aimed to identify herpes simplex virus (HSV) related biomarkers in periodontitis patients.

METHODS

The present study used DIA-based liquid chromatography-tandem mass spectrometry to analyze the proteome of human gingival fibroblasts (HGFs) from one healthy donor across early and late stages (12-72 h) of HSV-1 infection.

RESULTS

The study identified 890 differentially expressed proteins. At the early infection stage, there was a notable upregulation of proteins including interferon (IFN) regulatory factor 7, IFN-stimulated genes 15, interleukin 6 (IL6), toll-like receptor 2 (TLR2), and IFN-induced protein (IFI), alongside a downregulation of matrix metalloproteinase 2 (MMP2). We observed the activation of pathways, including the complement and coagulation cascades, lysosome, nucleotide-binding oligomerization domain-like receptors, retinoic acid-inducible gene I-like receptors, and TLR signaling pathways. Conversely, at the late stage, IFIs, IL1, and MMP3 were significantly upregulated, while complement proteins were downregulated. Biomarkers such as TLR2 may underscore the host's antiviral defense response to HSV-1 in the periodontal environment.

CONCLUSIONS

The present study identified several HGF proteins associated with periodontitis following HSV-1 infection, providing an analytical framework for determining the host's anti-viral defense response to antagonize HSV-1 infection in periodontal tissues.