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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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253124003317 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Cheryl Chan |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-f33ca153b30a486482b80163529e0dbe |
| institution | Kabale University |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-f33ca153b30a486482b80163529e0dbe2025-01-18T05:04:25ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-03-01361102444Extracellular viral microRNAs as biomarkers of virus infection in human cellsCheryl Chan0Joanne Xin Yi Loh1Wei-Xiang Sin2Denise Bei Lin Teo3Nicholas Kwan Zen Tan4Chandramouli Nagarajan5Yunxin Chen6Francesca Lorraine Wei Inng Lim7Michael E. Birnbaum8Rohan B.H. Williams9Stacy L. Springs10Critical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, SingaporeDepartment of Haematology, Singapore General Hospital, Singapore 169608, Singapore; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, Singapore; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, SingaporeDepartment of Haematology, Singapore General Hospital, Singapore 169608, Singapore; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, Singapore; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, SingaporeDepartment of Haematology, Singapore General Hospital, Singapore 169608, Singapore; SingHealth Duke-NUS Oncology Academic Clinical Programme, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, Singapore; SingHealth Duke-NUS Cell Therapy Centre, SingHealth Duke-NUS Academic Medical Centre, Singapore 168582, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA 02139, USACritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore; Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore 119077, SingaporeCritical Analytics for Manufacturing Personalized-Medicine, Singapore-MIT Alliance for Research and Technology, Singapore 138602, Singapore; Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Corresponding author: Stacy L. Springs, Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.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.http://www.sciencedirect.com/science/article/pii/S2162253124003317MT: Oligonucleotides: Diagnostics and Biosensorsvirus detectionvirus infectionextracellularplasmaviral microRNA |
| spellingShingle | 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 Extracellular viral microRNAs as biomarkers of virus infection in human cells Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Diagnostics and Biosensors virus detection virus infection extracellular plasma viral microRNA |
| title | Extracellular viral microRNAs as biomarkers of virus infection in human cells |
| title_full | Extracellular viral microRNAs as biomarkers of virus infection in human cells |
| title_fullStr | Extracellular viral microRNAs as biomarkers of virus infection in human cells |
| title_full_unstemmed | Extracellular viral microRNAs as biomarkers of virus infection in human cells |
| title_short | Extracellular viral microRNAs as biomarkers of virus infection in human cells |
| title_sort | extracellular viral micrornas as biomarkers of virus infection in human cells |
| topic | MT: Oligonucleotides: Diagnostics and Biosensors virus detection virus infection extracellular plasma viral microRNA |
| url | http://www.sciencedirect.com/science/article/pii/S2162253124003317 |
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