School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
Viruses. 2010 Jul;2(7):1382-1393. doi: 10.3390/v2071382. Epub 2010 Jul 5.
An important host factor for hepatitis C virus (HCV) is microRNA-122 (miR-122). miR-122 is a liver-specific member of a family of small, non-coding RNA molecules known as microRNAs that play major roles in the regulation of gene expression by direct interaction with RNA targets. miR-122 binds directly to two sites in the 5' untranslated region (UTR) of HCV RNA and positively regulates the viral life cycle. The mechanism by which this regulation occurs is still not fully understood. There has been a great deal of interest in potential therapeutics based on small RNAs, and targeting miR-122 to combat HCV is one of the furthest advanced. Chemical inhibitors of miR-122 can be introduced into mammals intravenously and result in potent and specific knockdown of the microRNA, with no detectable adverse effects on liver physiology. This strategy was recently applied to chimpanzees chronically infected with HCV and resulted in a sustained reduction in viral load in the animals. Inhibition of miR-122 therefore presents a very attractive novel approach to treating HCV, a virus for which improved therapeutics are urgently needed.
一种重要的丙型肝炎病毒（HCV）宿主因子是 microRNA-122（miR-122）。miR-122 是一类小的非编码 RNA 分子家族中的一种肝脏特异性成员，称为 microRNAs，它们通过与 RNA 靶标直接相互作用，在基因表达调控中发挥主要作用。miR-122 直接结合 HCV RNA 5'非翻译区（UTR）中的两个位点，并正向调节病毒生命周期。这种调节发生的机制尚不完全清楚。基于小 RNA 的潜在治疗方法引起了极大的兴趣，针对 miR-122 来对抗 HCV 是最先进的方法之一。miR-122 的化学抑制剂可以静脉内引入哺乳动物体内，导致微 RNA 有效且特异性地敲低，而对肝脏生理没有可检测到的不良影响。这一策略最近应用于慢性感染 HCV 的黑猩猩，导致动物体内病毒载量持续减少。因此，抑制 miR-122 为治疗 HCV 提供了一种非常有吸引力的新方法，因为迫切需要改善治疗方法。
