Abstract

Background: Herpes simplex viruses (HSV-1 & HSV-2) elicit numerous clinical manifestations in humans, such as skin lesions in the orofacial area and genitalia, as well as herpetic gingivostomatitis. Acyclovir, a nucleoside analogue commonly used to treat HSV infection is poorly effective for treating herpetic skin lesions when applied as a cream. Furthermore, acyclovir-resistant isolates have been isolated from immunosuppressed patients, thus requiring therapeutic alternatives. Cetylpyridinium chloride (CPC) is a quaternary ammonium compound with bactericidal properties that is frequently added to mouthwashes and deodorants; nevertheless it was recently reported to have virucidal activity against influenza A virus. Objectives: We sought to assess the potential antiviral effects of CPC against HSVs. Methods: Epithelial cells and human gingival fibroblasts were infected with HSV-1 or HSV-2 strains that express a green fluorescent protein (GFP) and then treated with CPC. Infection and viral processes were then followed within the infected cells. Results: We found that cells infected with HSV and then treated with CPC produced significantly less virus plaque forming units and displayed reduced expression of virus-encoded genes as compared to controls. Dissection of the viral step inhibited by CPC treatment indicates that CPC inhibits the transcription of viral gene early after infection by blocking the translocation of NF-κB to the nucleus of HSV-infected cells. Taken together, our results suggest that CPC has anti-HSV effects which is mediated by non-virucidal effects, but rather the modulation of cellular signalling events required by HSVs for replication.