Vaccine and Infectious Disease Organization/International Vaccine Center, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Liver Int. 2011 Nov;31(10):1449-67. doi: 10.1111/j.1478-3231.2011.02543.x. Epub 2011 May 5.
Hepatitis C viral protein translation occurs in a cap-independent manner through the use of an internal ribosomal entry site (IRES) present within the viral 5'-untranslated region. The IRES is composed of highly conserved structural domains that directly recruit the 40S ribosomal subunit to the viral genomic RNA. This frees the virus from relying on a large number of translation initiation factors that are required for cap-dependent translation, conferring a selective advantage to the virus especially in times when the availability of such factors is low. Although the mechanism of translation initiation on the Hepatitis C virus (HCV) IRES is well established, modulation of the HCV IRES activity by both cellular and viral factors is not well understood. As the IRES is essential in the HCV life cycle and as such remains well conserved in an otherwise highly heterogenic virus, the process of HCV protein translation represents an attractive target in the development of novel antivirals. This review will focus on the mechanisms of HCV protein translation and how this process is postulated to be modulated by cis-acting viral factors, as well as trans-acting viral and cellular factors. Numerous therapeutic approaches investigated in targeting HCV protein translation for the development of novel antivirals will also be discussed.
丙型肝炎病毒蛋白的翻译以一种帽非依赖性的方式发生，通过使用存在于病毒 5'非翻译区的内部核糖体进入位点（IRES）。IRES 由高度保守的结构域组成，这些结构域直接将 40S 核糖体亚基募集到病毒基因组 RNA 上。这使得病毒不再依赖于大量用于帽依赖性翻译的翻译起始因子，从而赋予病毒选择性优势，尤其是在这些因子供应不足的情况下。尽管丙型肝炎病毒（HCV）IRES 的翻译起始机制已经得到很好的阐明，但细胞和病毒因子对 HCV IRES 活性的调节还不是很清楚。由于 IRES 在 HCV 生命周期中是必不可少的，并且在高度异质的病毒中仍然保持高度保守，因此 HCV 蛋白翻译过程成为开发新型抗病毒药物的有吸引力的靶标。这篇综述将重点介绍 HCV 蛋白翻译的机制，以及该过程如何被顺式作用的病毒因子以及反式作用的病毒和细胞因子所调节。还将讨论为了开发新型抗病毒药物而针对 HCV 蛋白翻译进行的许多治疗方法的研究。
