Lighting up the Native Viral RNA Genome with a Fluorogenic Probe for the Live-Cell Visualization of Virus Infection

RNA viruses represent a major global health threat, and the visualization of their RNA genome in infected cells is essential for virological research and clinical diagnosis. Due to the lack of chemical toolkits for the live-cell imaging of viral RNA genomes, especially native viral genomes without l...

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Published in:Journal of the American Chemical Society 2019-04, Vol.141 (13), p.5182-5191
Main Authors: Luo, Xingyu, Xue, Binbin, Feng, Guangfu, Zhang, Jiaheng, Lin, Bin, Zeng, Pan, Li, Huiyi, Yi, Haibo, Zhang, Xiao-Lian, Zhu, Haizhen, Nie, Zhou
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container_issue 13
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container_title Journal of the American Chemical Society
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creator Luo, Xingyu
Xue, Binbin
Feng, Guangfu
Zhang, Jiaheng
Lin, Bin
Zeng, Pan
Li, Huiyi
Yi, Haibo
Zhang, Xiao-Lian
Zhu, Haizhen
Nie, Zhou
description RNA viruses represent a major global health threat, and the visualization of their RNA genome in infected cells is essential for virological research and clinical diagnosis. Due to the lack of chemical toolkits for the live-cell imaging of viral RNA genomes, especially native viral genomes without labeling and genetic modification, studies on native virus infection at the single-live-cell level are challenging. Herein, taking hepatitis C virus (HCV) as a representative RNA virus, we propose that the innate noncanonical G-quadruplex (G4) structure of viral RNA can serve as a specific imaging target and report a new benzothiazole-based G4-targeted fluorescence light-up probe, ThT-NE, for the direct visualization of the native RNA genome of HCV in living host cells. We demonstrate the use of the ThT-NE probe for several previously intractable applications, including the sensitive detection of individual virus-infected cells by small-molecule staining, real-time monitoring of the subcellular distribution of the viral RNA genome in live cells, and continuous live-cell tracking of the infection and propagation of clinically isolated native HCV. The fluorogenic-probe-based viral RNA light-up system opens up a promising chemical strategy for cutting-edge live-cell viral analysis, providing a potentially powerful tool for viral biology, medical diagnosis, and drug development.
doi_str_mv 10.1021/jacs.8b10265
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title Lighting up the Native Viral RNA Genome with a Fluorogenic Probe for the Live-Cell Visualization of Virus Infection
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