2′,5′-Oligoadenylate Synthetase in Interferon-α- and Acyclovir-Treated Herpes Simplex Virus-Infected Cells

Abstract

The 2′,5′-oligoadenylate (2-5A) synthetase pathway, induced by interferon-α (IFN-α), has been shown to be responsible for the antiviral action of IFN-α against some viruses. Studies were done to determine the role of this pathway in the anti—herpes simplex virus (HSV) action of IFN-α alone or in combination with acyclovir (ACV), a combination that leads to synergistic anti-HSV activity. Treatment of human corneal cells or Vero cells with 100 IU/ml of IFN-α induced expression of 2-5A synthetase mRNA and a 10-fold increase in 2-5A synthetase production compared with untreated cells. HSV infection alone did not induce 2-5A synthetase production, but when IFN-α-treated cells were infected with HSV, enzyme level was significantly increased (p < 0.05) compared with that in IFN-α-treated, uninfected cells. HSV infection actually decreased the level of 2-5A synthetase mRNA in IFN-α-treated cells. Although IFN-α treatment induced high levels of 2-5A synthetase with or without HSV infection, no activation of the latent endonuclease was detected by specific cleavage of ribosomal RNA. Treatment of infected cells with 5 μM ACV alone or combined with IFN-α did not increase 2-5A synthetase or endonuclease activities above those detected in cells not treated with ACV. The data indicate that the 2-5A synthetase pathway was inducible in corneal cells and Vero cells but did not appear to contribute to the anti-HSV activity of IFN-α alone or the synergistic activity of IFN-α combined with ACV.