Extracellular viral microRNAs as biomarkers of virus infection in human cells.

IF 6.1 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Therapy. Nucleic Acids Pub Date : 2024-12-31 eCollection Date: 2025-03-11 DOI:10.1016/j.omtn.2024.102444

Cheryl Chan, Joanne Xin Yi Loh, Wei-Xiang Sin, Denise Bei Lin Teo, Nicholas Kwan Zen Tan, Chandramouli Nagarajan, Yunxin Chen, Francesca Lorraine Wei Inng Lim, Michael E Birnbaum, Rohan B H Williams, Stacy L Springs

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Abstract

Nucleic acid amplification tests (NAATs) have enabled fast and sensitive detection of virus infections but are unable to discriminate between live and dead/inert viral fragments or between latent and reactivated virus infections. Here, we show that extracellular viral microRNAs (viral exmiRs) are cell-free candidate biomarkers of live, latent, and reactivated virus infections, achieving fast (under 1 day) and sensitive (30 attomolar [aM]) detection by quantitative real-time reverse transcription PCR (real-time RT-qPCR). We report that spent-media-derived Epstein-Barr virus (EBV) miR-BART10-3p and herpes simplex virus 1 (HSV-1) miR-H5 are biomarkers of live EBV-2 and HSV-1 infection of T cell cultures, respectively. We identified extracellular human herpesvirus 6 (HHV-6) miR-Ro6-4 as a biomarker of endogenous latent HHV-6 in healthy human donor T cell cultures and identified human cytomegalovirus (HCMV) miR-US5-2-5p and miR-US22-5p as plasma biomarkers of endogenous latent HCMV infection. Viral exmiR profiling of spent media from EBV- and HHV-8-reactivated B cell models revealed specific signatures of elevated EBV miR-BHRF1-2-3p and HHV-8 miR-K12-10a-3p, miR-K12-10b, and miR-K12-12-3p, respectively, during virus reactivation. Our study thus suggests the utility of viral exmiR biomarkers in enabling NAAT-based detection of live, endogenous latent, and reactivated virus infections of cells.

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细胞外病毒microrna作为人细胞病毒感染的生物标志物。

核酸扩增试验（NAATs）能够快速、灵敏地检测病毒感染，但不能区分活病毒和死病毒/惰性病毒片段，也不能区分潜伏病毒和再激活病毒感染。在这里，我们发现细胞外病毒microRNAs（病毒exmir）是活的、潜伏的和再激活的病毒感染的无细胞候选生物标志物，通过定量实时反转录PCR （real-time RT-qPCR）实现快速（不到1天）和敏感（30原子摩尔[aM]）的检测。我们报道，花培养基衍生的eb病毒（EBV） miR-BART10-3p和单纯疱疹病毒1 (HSV-1) miR-H5分别是活的EBV-2和HSV-1感染T细胞培养物的生物标志物。我们在健康的人供体T细胞培养中鉴定出细胞外人疱疹病毒6 (HHV-6) miR-Ro6-4是内源性潜伏HHV-6的生物标志物，鉴定出人巨细胞病毒（HCMV） miR-US5-2-5p和miR-US22-5p是内源性潜伏HCMV感染的血浆生物标志物。对EBV-和HHV-8再激活的B细胞模型的乏培养基进行病毒exmiR分析，发现在病毒再激活期间，EBV miR-BHRF1-2-3p和HHV-8 miR-K12-10a-3p、miR-K12-10b和miR-K12-12-3p的特异性特征分别升高。因此，我们的研究表明，病毒exmiR生物标志物在基于naat的活病毒、内源性潜伏病毒和再激活病毒感染细胞检测中的应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

15.40

自引率

1.10%

发文量

336

审稿时长

20 weeks

期刊介绍： Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.