Inhibition of herpes simplex virus type 1, respiratory syncytial virus and echovirus type 11 by peroxidase-generated hypothiocyanite.
The human mouth is an important route of viral transmission and evidence exists that human saliva can neutralize some viruses, e.g. herpes simplex type 1 (HSV-1) and human immunodeficiency virus (HIV) in vitro. However, little is known of the actual antiviral agents in saliva. We have analyzed how hypothiocyanite (HOSCN/-OSCN) ions, present in human saliva and generated by salivary peroxidase systems, affect the viability of three different types of viruses; HSV-1 (capable of inducing oral lesions), respiratory syncytial virus (RSV, respiratory infections), and echovirus 11 (EV 11, enteric diseases). Viral suspensions were pretreated (30 min) with HOSCN/-OSCN concentrations up to 180 microM both at pH 6.0 and 7.1 and inoculated into human gingival fibroblasts. The cultures were incubated at 37 degrees C for 18-48 h, fixed and the infected cells were counted after immunoperoxidase staining. HSV-1 was most sensitive to HOSCN/-OSCN with an IC50 of 8.5 microM at pH 6.0 and an IC50 of 20 microM at pH 7.1, respectively. RSV was inhibited by HOSCN/-OSCN only at pH 6.0 with an IC50 of 8.0 microM. EV 11 was also resistant at neutral pH, but sensitive at pH 6.0 with an IC50 of 68 microM. In contrast to HSV-1 and RSV, the inhibition of EV 11 was not dependent on the concentration of HOSCN/-OSCN. The inhibition was in all cases stronger at pH 6.0 than at neutral pH. Our results suggest that hypothiocyanite, a normal component of human whole saliva, in physiological concentrations effectively inhibits HSV-1 and RSV at acidic pH, whereas EV 11 is more resistant in vitro.
Mikola
H
H
Department of Cariology, University of Turku, Finland.
Waris
M
M
Tenovuo
J
J
D000328:Adult; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D029822:Enterovirus B, Human / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D005881:Gingiva / Q000166:cytology; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007124:Immunoenzyme Techniques; D009195:Peroxidase / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D012463:Saliva / Q000201:enzymology / Q000821:virology; D013861:Thiocyanates / Q000378:metabolism / Q000494:pharmacology*
D000998:Antiviral Agents; D013861:Thiocyanates; C014607:hypothiocyanite ion; D009195:Peroxidase