Complex role of microRNAs in HTLV-1 infections.
Complex role of microRNAs in HTLV-1 infections.
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DOI：
10.3389/fgene.2012.00295
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发表时间：
2012
影响因子：
3.7
通讯作者：
Kashanchi F
中科院分区：
文献类型：
--
作者：
Sampey GC;Van Duyne R;Currer R;Das R;Narayanan A;Kashanchi F
人类嗜T淋巴细胞病毒1（HTLV-1）是第一个被发现的人类逆转录病毒，并且是成人T细胞白血病/淋巴瘤（ATL）和神经退行性疾病HTLV-1相关的脊髓病/热带痉挛性轻瘫（HAM/TSP）的病原体。microRNA（miRNA）在其他几种病毒的复制周期中以及在相关病理学进展中的重要性在过去十年中已经得到了很好的确立。此外，miRNA改变参与HTLV-1的生命周期，并在其相关的致癌性和神经退行性疾病的进展，最近已经曝光。几种HTLV-1衍生的蛋白质改变转录因子功能，与染色质重塑剂相互作用，或操纵RNA干扰（RNAi）机制的组分，从而建立多种途径，通过这些途径可以在宿主细胞中上调或下调miRNA表达。此外，宿主miRNA的失调通过其影响HTLV-1感染的细胞的作用机制可以显著变化，并且包括经由RNA诱导的沉默复合物（RISC）的mRNA沉默、转录基因沉默、RNAi组分的抑制和染色质重塑。这些miRNA诱导的变化可导致细胞存活、侵袭、增殖和分化增加，以及允许病毒潜伏。虽然最近的许多研究已经成功地将miRNA与HTLV-1感染的生命周期和发病机制联系起来，但仍有一些重要的悬而未决的问题需要解决。在这里，我们将回顾最近的发现阐明HTLV-1介导的宿主细胞miRNA谱的操纵，并检查对发病机制的影响，以及探索未来的调查路线，可以增加在这一研究领域的理解。
Human T-lymphotropic virus 1 (HTLV-1) was the first human retrovirus to be discovered and is the causative agent of adult T-cell leukemia/lymphoma (ATL) and the neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The importance of microRNA (miRNA) in the replicative cycle of several other viruses, as well as in the progression of associated pathologies, has been well established in the past decade. Moreover, involvement of miRNA alteration in the HTLV-1 life cycle, and in the progression of its related oncogenic and neurodegenerative diseases, has recently come to light. Several HTLV-1 derived proteins alter transcription factor functionalities, interact with chromatin remodelers, or manipulate components of the RNA interference (RNAi) machinery, thereby establishing various routes by which miRNA expression can be up- or down-regulated in the host cell. Furthermore, the mechanism of action through which dysregulation of host miRNAs affects HTLV-1 infected cells can vary substantially and include mRNA silencing via the RNA-induced silencing complex (RISC), transcriptional gene silencing, inhibition of RNAi components, and chromatin remodeling. These miRNA-induced changes can lead to increased cell survival, invasiveness, proliferation, and differentiation, as well as allow for viral latency. While many recent studies have successfully implicated miRNAs in the life cycle and pathogenesis of HTLV-1 infections, there are still significant outstanding questions to be addressed. Here we will review recent discoveries elucidating HTLV-1 mediated manipulation of host cell miRNA profiles and examine the impact on pathogenesis, as well as explore future lines of inquiry that could increase understanding in this field of study.