Branch Andrea D, Stump Decherd D, Gutierrez Julio A, Eng Francis, Walewski José L
Division of Liver Diseases, Mount Sinai School of Medicine, New York, NY 10029, USA.
Semin Liver Dis. 2005 Feb;25(1):105-17. doi: 10.1055/s-2005-864786.
The hepatitis C virus (HCV) has an alternate reading frame (ARF) that overlaps the core protein gene. The overlapping reading frame distinguishes HCV from all of its known viral relatives, with the possible exception of GB virus B (GBV-B). The ARF is expressed during natural HCV infections and stimulates specific immune responses. Like several essential genes in other viruses (e.g., the human immunodeficiency virus polymerase) the ARF lacks an in-frame AUG start codon, suggesting that its expression involves unusual translation-level events. In vitro studies indicate that ribosomal frameshifting may be one of several processes that can lead to translation of the ARF. Frameshifting yields chimeric proteins that have segments encoded in the core gene covalently attached to amino acids encoded in the ARF. A consistent nomenclature for the ARF's protein products has yet to be established. We propose that all proteins that contain amino acids encoded in the + 1 ARF be called alternate reading frame proteins (ARFPs) and that specific ARFPs, such as the ARFP/F-protein, the double-frameshift protein, and the short form of core + 1, be designated as follows: ARFP/F (ARFP/F-protein), ARFP/DF (double-frameshift), and ARFP/S (short form of core + 1). The roles of ARFPs in the HCV life cycle are not yet known. There is a significant possibility that ARFPs may be responsible for some of the effects attributed to the core protein, given that most studies seeking to define the function of the core protein have employed materials likely to contain a combination of the core protein and ARFPs. The observed effects of the core protein include the induction of liver cancer, transformation of cells, and alterations of immune responses. This article reviews the discovery of ARF, describes the RNA structural elements involved in core/ARF gene expression, discusses possible functions of ARFPs, and considers the potential usefulness of ARFPs in vaccines. The HCV ARF is the focus of a new and rapidly expanding area of research, and the results of many ongoing studies are currently available in abstract form only. The preliminary nature of investigations that have not yet been reviewed by peers is noted in the text.
丙型肝炎病毒（HCV）有一个与核心蛋白基因重叠的交替阅读框（ARF）。这种重叠阅读框使HCV有别于所有已知的病毒亲属，GB病毒B（GBV - B）可能除外。ARF在自然HCV感染过程中表达，并刺激特定的免疫反应。与其他病毒中的几个必需基因（例如人类免疫缺陷病毒聚合酶）一样，ARF缺乏符合读框的AUG起始密码子，这表明其表达涉及异常的翻译水平事件。体外研究表明，核糖体移码可能是导致ARF翻译的几种过程之一。移码产生嵌合蛋白，其具有在核心基因中编码的片段与在ARF中编码的氨基酸共价连接。ARF的蛋白质产物尚未建立一致的命名法。我们建议将所有包含在+1 ARF中编码的氨基酸的蛋白质称为交替阅读框蛋白（ARFP），并且特定的ARFP，如ARFP/F蛋白、双移码蛋白和核心+1的短形式，应按如下方式命名：ARFP/F（ARFP/F蛋白）、ARFP/DF（双移码）和ARFP/S（核心+1的短形式）。ARFP在HCV生命周期中的作用尚不清楚。鉴于大多数试图定义核心蛋白功能的研究使用的材料可能同时包含核心蛋白和ARFP，ARFP很有可能是一些归因于核心蛋白的效应的原因。核心蛋白观察到的效应包括肝癌的诱导、细胞转化和免疫反应的改变。本文回顾了ARF的发现，描述了参与核心/ARF基因表达的RNA结构元件，讨论了ARFP的可能功能，并考虑了ARFP在疫苗中的潜在用途。HCV ARF是一个新的且迅速扩展的研究领域的焦点，许多正在进行的研究结果目前仅以摘要形式提供。文中指出了尚未经过同行评审的研究的初步性质。
