Anti-HIV-1 Effect of the Fluoroquinolone Enoxacin and Modulation of Pro-Viral hsa-miR-132 Processing in CEM-SS Cells.

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Non-Coding RNA Pub Date : 2025-01-20 DOI:10.3390/ncrna11010008

Verena Schlösser, Helen Louise Lightfoot, Christine Leemann, Seyedeh Elnaz Banijamali, Aathma Merin Bejoy, Shashank Tiwari, Jeffrey L Schloßhauer, Valentina Vongrad, Andreas Brunschweiger, Jonathan Hall, Karin J Metzner, Jochen Imig

{"title":"Anti-HIV-1 Effect of the Fluoroquinolone Enoxacin and Modulation of Pro-Viral hsa-miR-132 Processing in CEM-SS Cells.","authors":"Verena Schlösser, Helen Louise Lightfoot, Christine Leemann, Seyedeh Elnaz Banijamali, Aathma Merin Bejoy, Shashank Tiwari, Jeffrey L Schloßhauer, Valentina Vongrad, Andreas Brunschweiger, Jonathan Hall, Karin J Metzner, Jochen Imig","doi":"10.3390/ncrna11010008","DOIUrl":null,"url":null,"abstract":"Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between HIV-1 infection and changes of the intrinsic cellular miRNA milieu. This interrelationship may direct potential alterations of the host cells' environment beneficial for the virus or its suppression of replication. Whether this tightly balanced and controlled battle can be exploited therapeutically remains to be further addressed. In this context, the fluoroquinolone antibiotic Enoxacin has been demonstrated as a potent modulator of miRNA processing. Here, we test the hypothesis that this applies also to selected HIV-1-related miRNAs.Methods: We studied the effect of Enoxacin on HIV-1 replication coupled with miRNA qRT-PCR analysis of HIV-1-related miRNAs in CEM-SS and MT-4 T-cells. The effects of miRNA mimic transfections combined with Enoxacin treatment on HIV-1 replication were assessed. Finally, we employed an in vitro DICER1 cleavage assay to study the effects of Enoxacin on a pro-HIV-1 miRNA hsa-miR-132 processing.Results: We established that Enoxacin, but not the structurally similar compound nalidixic acid, exhibits strong anti-HIV-1 effects in the T-cell line CEM-SS, but not MT-4. We provide experimental data that this effect of Enoxacin is partly attributed to the specific downregulation of mature hsa-miR-132-3p, but not other tested pro- or anti-HIV-1 miRNAs, which is likely due to affecting DICER1 processing.Conclusions: Our findings show an anti-retroviral activity of Enoxacin at least in part by downregulation of hsa-miR-132-3p, which may be relevant for future antiviral therapeutic applications by modulation of the RNA interference pathway.","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"11 1","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755467/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Non-Coding RNA","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/ncrna11010008","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between HIV-1 infection and changes of the intrinsic cellular miRNA milieu. This interrelationship may direct potential alterations of the host cells' environment beneficial for the virus or its suppression of replication. Whether this tightly balanced and controlled battle can be exploited therapeutically remains to be further addressed. In this context, the fluoroquinolone antibiotic Enoxacin has been demonstrated as a potent modulator of miRNA processing. Here, we test the hypothesis that this applies also to selected HIV-1-related miRNAs.

Methods: We studied the effect of Enoxacin on HIV-1 replication coupled with miRNA qRT-PCR analysis of HIV-1-related miRNAs in CEM-SS and MT-4 T-cells. The effects of miRNA mimic transfections combined with Enoxacin treatment on HIV-1 replication were assessed. Finally, we employed an in vitro DICER1 cleavage assay to study the effects of Enoxacin on a pro-HIV-1 miRNA hsa-miR-132 processing.

Results: We established that Enoxacin, but not the structurally similar compound nalidixic acid, exhibits strong anti-HIV-1 effects in the T-cell line CEM-SS, but not MT-4. We provide experimental data that this effect of Enoxacin is partly attributed to the specific downregulation of mature hsa-miR-132-3p, but not other tested pro- or anti-HIV-1 miRNAs, which is likely due to affecting DICER1 processing.

Conclusions: Our findings show an anti-retroviral activity of Enoxacin at least in part by downregulation of hsa-miR-132-3p, which may be relevant for future antiviral therapeutic applications by modulation of the RNA interference pathway.

查看原文本刊更多论文

氟喹诺酮依诺沙星在CEM-SS细胞中的抗hiv -1作用及对前病毒hsa-miR-132加工的调节

背景：尽管针对HIV-1感染的抗逆转录病毒疗法（ART）取得了巨大进展，但目前还没有治愈方法或疫苗接种。因此，发现新的治疗策略仍然是迫切需要的。从这个意义上说，miRNA和miRNA疗法已经成为最近hiv -1相关研究的重点。HIV-1感染与内在细胞miRNA环境的变化之间存在着强烈的相互依赖关系。这种相互关系可能指导宿主细胞环境的潜在改变，使其有利于病毒或抑制病毒复制。这种紧密平衡和控制的战斗能否用于治疗还有待进一步研究。在这种情况下，氟喹诺酮类抗生素依诺沙星已被证明是miRNA加工的有效调节剂。在这里，我们验证了这一假设，即这也适用于选定的hiv -1相关mirna。方法：研究依诺沙星对HIV-1复制的影响，并结合miRNA qRT-PCR分析CEM-SS和MT-4 t细胞中HIV-1相关miRNA。评估miRNA模拟转染联合依诺沙星治疗对HIV-1复制的影响。最后，我们采用体外DICER1切割实验来研究依诺沙星对亲hiv -1 miRNA hsa-miR-132加工的影响。结果：我们确定了依诺沙星，而不是结构相似的化合物萘啶酸，在t细胞系CEM-SS中表现出很强的抗hiv -1作用，而在MT-4中没有。我们提供的实验数据表明，依诺沙星的这种作用部分归因于成熟的hsa-miR-132-3p的特异性下调，而不是其他测试的亲或抗hiv -1 miRNAs，这可能是由于影响DICER1加工。结论：我们的研究结果表明，依诺沙星的抗逆转录病毒活性至少部分是通过下调hsa-miR-132-3p来实现的，这可能与未来通过调节RNA干扰途径进行抗病毒治疗有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

6.70

自引率

4.70%

发文量

审稿时长

10 weeks

期刊介绍： Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.