Taylor J L, Witt P L, Irizarry A, Tom P, O'Brien W J
Department of Microbiology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Interferon Cytokine Res. 1995 Jan;15(1):27-30. doi: 10.1089/jir.1995.15.27.
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.
由α-干扰素（IFN-α）诱导的2',5'-寡腺苷酸（2-5A）合成酶途径已被证明负责IFN-α对某些病毒的抗病毒作用。开展了多项研究以确定该途径在IFN-α单独或与阿昔洛韦（ACV）联合使用时对单纯疱疹病毒（HSV）的作用中的角色，IFN-α与ACV联合使用可产生协同抗HSV活性。用100 IU/ml的IFN-α处理人角膜细胞或非洲绿猴肾细胞（Vero细胞），与未处理的细胞相比，可诱导2-5A合成酶mRNA的表达，且2-5A合成酶产量增加10倍。单独的HSV感染不会诱导2-5A合成酶的产生，但当用IFN-α处理过的细胞感染HSV时，与经IFN-α处理但未感染的细胞相比，酶水平显著升高（p < 0.05）。实际上，HSV感染降低了经IFN-α处理的细胞中2-5A合成酶mRNA的水平。尽管无论有无HSV感染，IFN-α处理均可诱导高水平的2-5A合成酶，但通过核糖体RNA的特异性切割未检测到潜伏性核酸内切酶的激活。用5 microM的ACV单独或与IFN-α联合处理感染的细胞，2-5A合成酶或核酸内切酶活性并未高于未用ACV处理的细胞中检测到的活性。数据表明，2-5A合成酶途径在角膜细胞和Vero细胞中可被诱导，但似乎对IFN-α单独的抗HSV活性或IFN-α与ACV联合的协同活性没有贡献。
