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微小 RNA 与 HIV-1 感染:抗病毒作用及其他。

MicroRNAs and HIV-1 infection: antiviral activities and beyond.

机构信息

Graduate Program in Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA; Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.

Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA.

出版信息

J Mol Biol. 2014 Mar 20;426(6):1178-97. doi: 10.1016/j.jmb.2013.12.017. Epub 2013 Dec 25.

Abstract

Cellular microRNAs (miRNAs) are an important class of small, non-coding RNAs that bind to host mRNAs based on sequence complementarity and regulate protein expression. They play important roles in controlling key cellular processes including cellular inception, differentiation and death. While several viruses have been shown to encode for viral miRNAs, controversy persists over the expression of a functional miRNA encoded in the human immunodeficiency virus type 1 (HIV-1) genome. However, it has been reported that HIV-1 infectivity is influenced by cellular miRNAs. Either through directly targeting the viral genome or by targeting host cellular proteins required for successful virus replication, multiple cellular miRNAs seem to modulate HIV-1 infection and replication. Perhaps as a survival strategy, HIV-1 may modulate proteins in the miRNA biogenesis pathway to subvert miRNA-induced antiviral effects. Global expression profiles of cellular miRNAs have also identified alterations of specific miRNAs post-HIV-1 infection both in vitro and in vivo (in various infected patient cohorts), suggesting potential roles for miRNAs in pathogenesis and disease progression. However, little attention has been devoted in understanding the roles played by these miRNAs at a cellular level. In this manuscript, we review past and current findings pertaining to the field of miRNA and HIV-1 interplay. In addition, we suggest strategies to exploit miRNAs therapeutically for curbing HIV-1 infectivity, replication and latency since they hold an untapped potential that deserves further investigation.

摘要

细胞 microRNAs (miRNAs) 是一类重要的小非编码 RNA,它们基于序列互补性与宿主 mRNAs 结合,从而调节蛋白质表达。它们在控制包括细胞起始、分化和死亡在内的关键细胞过程中发挥着重要作用。虽然已经发现几种病毒编码了病毒 miRNAs,但人类免疫缺陷病毒 1 (HIV-1) 基因组中编码功能性 miRNA 的表达仍然存在争议。然而,据报道,细胞 miRNAs 会影响 HIV-1 的感染性。通过直接靶向病毒基因组或靶向宿主细胞中成功复制病毒所需的蛋白质,多种细胞 miRNAs 似乎可以调节 HIV-1 的感染和复制。也许作为一种生存策略,HIV-1 可能会调节 miRNA 生物发生途径中的蛋白质,以颠覆 miRNA 诱导的抗病毒作用。细胞 miRNAs 的全局表达谱也在体外和体内(在各种感染患者队列中)鉴定出 HIV-1 感染后特定 miRNAs 的改变,这表明 miRNAs 在发病机制和疾病进展中可能具有潜在作用。然而,人们很少关注这些 miRNAs 在细胞水平上所起的作用。在本文中,我们回顾了 miRNA 和 HIV-1 相互作用领域的过去和当前研究结果。此外,我们还提出了利用 miRNAs 进行治疗以抑制 HIV-1 感染性、复制和潜伏期的策略,因为它们具有未被开发的潜力,值得进一步研究。

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