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

Baskin H., Yazici Z., BAŞBINAR Y., Olgun N., ÖZKUL A., Hakki Bahar I.

NEW MICROBIOLOGICA, cilt.28, sa.3, ss.205-213, 2005 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Sayı: 3
  • Basım Tarihi: 2005
  • Dergi Adı: NEW MICROBIOLOGICA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.205-213
  • Anahtar Kelimeler: acyclovir, HSV-1, HSV-2, nitric oxide, apoptosis, necrosis, SIMPLEX-VIRUS TYPE-1, PURINE NUCLEOSIDE ANALOGS, BRAIN-TISSUE, APOPTOSIS, BLOCKS, ENCEPHALITIS, GANCICLOVIR, PENCICLOVIR, INHIBITION, EXPRESSION
  • Dokuz Eylül Üniversitesi Adresli: Evet

Özet

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 HEp2 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 mu g/mL) of ACV. In 48.8, 24.4 and 12.2 mu g/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 mu g/mL of ACV HSV-1 had a "downregulating 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 mu g/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 mu g/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 mu g/mL of ACV, HSV-1 had significant "necrotic effect" on necrotic cellular death, "necrosis" increased in 12.2, 6.1, 3 and 1.5 mu g/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 apoptosishiecrosis 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.