2',5'-oligoadenylate synthetase in interferon-alpha- and acyclovir-treated herpes simplex virus-infected cells

The 2',5'-oligoadenylate (2-5A) synthetase pathway, induced by interferon-alpha (IFN-alpha), has been shown to be responsible for the antiviral action of IFN-alpha against some viruses. Studies were done to determine the role of this pathway in the anti-herpes simplex virus (HSV) action of IFN-alpha 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-alpha 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-alpha-treated cells were infected with HSV, enzyme level was significantly increased (p < 0.05) compared with that in IFN-alpha-treated, uninfected cells. HSV infection actually decreased the level of 2-5A synthetase mRNA in IFN-alpha-treated cells. Although IFN-alpha 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 microM ACV alone or combined with IFN-alpha 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-alpha alone or the synergistic activity of IFN-alpha combined with ACV.