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microRNAs 在 HIV-1 发病机制和治疗中的作用。

The role of microRNAs in HIV-1 pathogenesis and therapy.

机构信息

Immunovirology Laboratory, St Vincent's Centre for Applied Medical Research, Kirby Institute, University of New South Wales, Sydney, Australia.

出版信息

AIDS. 2012 Jul 17;26(11):1325-34. doi: 10.1097/QAD.0b013e328352adca.

Abstract

There has been a paradigm shift in our understanding of how protein regulation occurs within mammalian cells in the last 15 years. Our current understanding is that small, noncoding RNA molecules called microRNAs (miRNAs) play a vital role in modulating the translation of mRNAs into protein. Important studies suggest that HIV-1 replication may be restricted by certain host cellular miRNAs, and this in turn may play pivotal roles in host defense and in maintaining latency within resting CD4 T cells. Conversely, host cellular miRNAs have also been demonstrated to be essential for certain viruses to establish infection and the altered expression of cellular miRNAs in the setting of HIV-1 may also be a factor favoring viral replication. The differential expression of important protective histocompatability locus antigen (HLA) alleles in HIV-1 infection has recently been shown to be regulated by miRNAs. To date, most efforts into finding an effective vaccine to combat HIV-1 have not been successful. Understanding the role that miRNAs may play in HIV-1 pathogenesis may allow a different approach to targeting key small RNAs or the identification of new important protein targets regulated by miRNAs, which may result in a better vaccine construct. The purpose of this review is to look at our current state of understanding of how HIV-1 and the miRNA pathway interact and the possible therapeutic interventions that this knowledge may entail.

摘要

在过去的 15 年中,我们对哺乳动物细胞中蛋白质调控方式的理解发生了重大转变。我们目前的认识是,称为 microRNAs(miRNAs)的小非编码 RNA 分子在调节 mRNA 翻译成蛋白质方面发挥着重要作用。重要的研究表明,HIV-1 的复制可能受到某些宿主细胞 miRNA 的限制,而这反过来又可能在宿主防御和维持静止 CD4 T 细胞潜伏期方面发挥关键作用。相反,宿主细胞 miRNA 对于某些病毒的感染也是必不可少的,并且在 HIV-1 感染中细胞 miRNA 的表达改变也可能是促进病毒复制的一个因素。重要的组织相容性位点抗原(HLA)等位基因在 HIV-1 感染中的差异表达最近被证明受到 miRNA 的调控。迄今为止,大多数针对 HIV-1 的有效疫苗的研究都没有成功。了解 miRNA 在 HIV-1 发病机制中可能发挥的作用,可以采用不同的方法来靶向关键的小 RNA 或鉴定受 miRNA 调控的新的重要蛋白靶标,这可能会产生更好的疫苗构建。本文的目的是探讨我们目前对 HIV-1 与 miRNA 通路相互作用的理解,以及这一知识可能带来的治疗干预措施。

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