Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus
Members of the NF90/NFAR protein group are involved in the life cycle of a positive-strand RNA virus
复制标题
DOI：
10.1093/emboj/cdg562
复制
发表时间：
2003-11-03
期刊：
影响因子：
11.4
通讯作者：
Behrens, SE
中科院分区：
文献类型：
--
作者：
Isken, O;Grassmann, CW;Behrens, SE
当前病毒学的一个主要问题涉及作为病毒增殖过程的功能组分的细胞蛋白的表征。在这里，我们描述了一组宿主因子命名为“NFAR蛋白”，是由牛病毒性腹泻病毒，人类病原体丙型肝炎病毒的近亲的复制机制招募。NFAR蛋白与病毒RNA基因组的两个末端特异性结合，涉及5'和3'非翻译区中的调控元件。3'非翻译区中蛋白质相互作用位点的修饰产生复制缺陷的病毒RNA。病毒复制也受到RNAi方法的抑制，该方法降低了宿主细胞细胞质中RNA解旋酶A（NFAR组成员）的浓度。进一步的实验数据表明，NFAR蛋白介导的病毒基因组的环状构象，这可能是重要的翻译和复制的协调。由于NFAR蛋白被认为是抗病毒反应的组成部分，我们怀疑病毒募集也可能削弱细胞防御机制。
A major issue of current virology concerns the characterization of cellular proteins that operate as functional components of the viral multiplication process. Here we describe a group of host factors designated as 'NFAR proteins' that are recruited by the replication machinery of bovine viral diarrhea virus, a close relative of the human pathogen hepatitis C virus. The NFAR proteins associate specifically with both the termini of the viral RNA genome involving regulatory elements in the 5' and 3' non-translated regions. Modification of the protein interaction sites in the 3' non-translated region yielded viral RNAs that were replication deficient. Viral replication was also inhibited by RNAi approaches that reduced the concentration of RNA helicase A, a member of the NFAR group, in the host cell's cytoplasm. Further experimental data suggest that NFAR proteins mediate a circular conformation of the viral genome that may be important for the coordination of translation and replication. Because NFAR proteins are presumed components of the antiviral response, we suspect that viral recruitment may also serve to weaken cellular defense mechanisms.