Extracellular viral microRNAs as biomarkers of virus infection in human cells

Extracellular viral microRNAs as biomarkers of virus infection in human cells

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 ce...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: Oligonucleotides: Diagnostics and Biosensors
virus detection
virus infection
extracellular
plasma
viral microRNA
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253124003317
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Summary: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.
ISSN:2162-2531

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