Martinand C, Salehzada T, Silhol M, Lebleu B, Bisbal C
IGMM UMR-CNRS 5535-Université Montpellier II, France.
J Interferon Cytokine Res. 1998 Dec;18(12):1031-8. doi: 10.1089/jir.1998.18.1031.
The (2-5A)-RNase L pathway is an important component of interferon (IFN) action. Its central role in the antiviral effect of IFN against Picornaviridae has been clearly demonstrated. We have characterized and cloned a new component of this pathway, the RNase L inhibitor (RLI). RLI is a cellular protein whose mRNA is not regulated by IFN but is induced by viruses, such as encephalomyocarditis virus (EMCV). RLI inhibits RNase L during the time course of EMCV infection, and overexpression of RLI in HeLa cells partially reverses the antiviral action of IFN against EMCV. The replicative complexes of several viruses consist of double-stranded RNA structures. These dsRNAs could activate gene transcription as demonstrated for IFNs and could be responsible for RLI induction. We describe the increased expression of RLI mRNA and RLI protein induced by synthetic dsRNAs, such as poly(I):poly(C). This induction gives rise to an inhibition of the 2-5A-binding activity of RNase L. The inhibition of RNase L activity is transcient, probably due to the rapid turnover of RLI protein.
（2-5A）-核糖核酸酶L途径是干扰素（IFN）作用的一个重要组成部分。其在IFN抗小核糖核酸病毒科病毒的抗病毒作用中的核心作用已得到明确证实。我们已经鉴定并克隆了该途径的一个新成分，即核糖核酸酶L抑制剂（RLI）。RLI是一种细胞蛋白，其mRNA不受IFN调控，但可被病毒诱导，如脑心肌炎病毒（EMCV）。在EMCV感染过程中，RLI会抑制核糖核酸酶L，并且在HeLa细胞中过表达RLI可部分逆转IFN对EMCV的抗病毒作用。几种病毒的复制复合体由双链RNA结构组成。这些双链RNA如IFN那样可激活基因转录，并且可能是RLI诱导产生的原因。我们描述了由合成双链RNA如聚肌苷酸：聚胞苷酸（poly(I):poly(C)）诱导的RLI mRNA和RLI蛋白表达增加。这种诱导导致核糖核酸酶L的2-5A结合活性受到抑制。核糖核酸酶L活性的抑制是短暂的，这可能是由于RLI蛋白的快速周转所致。
