Effects of non toxic doses of acyclovir on nitric oxide and cellular death responses in herpesvirus types 1 and 2 infected hep-2 cells

• Published in: The New microbiologica Vol. 28; no. 3; p. 205
• Main Authors: Baskin, Huseyin, Yazici, Zafer, Baskin, Yasemin, Olgun, Nur, Ozkul, Aykut, Bahar, I Hakki
• Format: Journal Article
• Language: English
• Published: Italy 01.07.2005
• Subjects: Acyclovir - pharmacology; Antiviral Agents - pharmacology; Apoptosis - drug effects; Cell Death - drug effects; Cell Line, Tumor; Cytopathogenic Effect, Viral; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Epithelial Cells - virology; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - physiology; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - physiology; Humans; Necrosis; Nitric Oxide - metabolism
• ISSN: 1121-7138

Herpes simplex virus type-1 (HSV-1) and type-2 (HSV-2) are among the most "successful" pathogens and code for a variety of proteins to direct the apoptosis/necrosis responses of the cells they infect. Nitric oxide (NO) is an important intracellular signaling molecule in pathological processes. Acyclovir (ACV) is a chain terminator that targets the viral DNA polymerase as an antiviral agent. In this study, NO signals, and apoptosis/necrosis responses of HEp-2 cells were compared when infected by HSV-1 and -2 for 24 hours against non toxic doses (starting from 48.8, 24.4, 12.2, 6.1, 3 to 1.5 microg/mL) of ACV. In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "upregulating effect" whereas HSV-2 had a "downregulating effect" on NO production, and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had a "down-regulating effect" whereas HSV-2 had an "upregulating effect" on NO responses (HSV-1 had a "downregulating effect" on NO production whereas HSV-2 had an "upregulating effect" on NO production without any ACV). In 48.8, 24.4 and 12.2 microg/mL of ACV, HSV-1 had an "anti-apoptotic effect" whereas HSV-2 had a stimulation on "apoptotic effect", and in 6.1, 3 and 1.5 microg/mL of ACV HSV-1 had an "apoptotic effect" and HSV-2 turned to "its natural viral apoptotic effect level" (HSV-1 had an "natural viral apoptotic effect" whereas HSV-2 had a "natural viral apoptotic effect" on apoptosis response without any ACV). In 48.8, and 24.4 microg/mL of ACV, HSV-1 had significant "necrotic effect" on necrotic cellular death, "necrosis" increased in 12.2, 6.1, 3 and 1.5 microg/mL of ACV (HSV-1 had a negligible "necrotic effect" on HEp-2 cells alone), and HSV-2 had a "natural viral necrotic effect" alone; and also in all non toxic ACV concentrations. These results showed that HSV-1 and -2 had different "strategies" on apoptosis/necrosis and NO with and without non toxic ACV. These differences deserve further studies in order to explain the interactions between apoptotic/anti apoptotic, necrotic genes and NO, and ACV in HSV-1 and HSV-2 infections respectively.