Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies
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Viral genome imaging.pdf
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Author(s)
Luna, Joseph M.
Hoffmann, Hans.-Heinrich
Espiritu, Christine
Sheahan, Timothy P.
Rice, Charles M.
Ramanan, Vyas
Trehan, Kartik
Ong, Mei Lyn
Chandrasekar, Hamsika
Christine, Kathleen
Date Issued
April 2016
Journal
Virology
Publisher
Elsevier
Citation
Ramanan, Vyas et al. “Viral Genome Imaging of Hepatitis C Virus to Probe Heterogeneous Viral Infection and Responses to Antiviral Therapies.” Virology 494 (2016): 236–247.
Version
Author's final manuscript
Abstract
Hepatitis C virus (HCV) is a positive single-stranded RNA virus of enormous global health importance, with direct-acting antiviral therapies replacing an immunostimulatory interferon-based regimen. The dynamics of HCV positive and negative-strand viral RNAs (vRNAs) under antiviral perturbations have not been studied at the single-cell level, leaving a gap in our understanding of antiviral kinetics and host–virus interactions. Here, we demonstrate quantitative imaging of HCV genomes in multiple infection models, and multiplexing of positive and negative strand vRNAs and host antiviral RNAs. We capture the varying kinetics with which antiviral drugs with different mechanisms of action clear HCV infection, finding the NS5A inhibitor daclatasvir to induce a rapid decline in negative-strand viral RNAs. We also find that the induction of host antiviral genes upon interferon treatment is positively correlated with viral load in single cells. This study adds smFISH to the toolbox available for analyzing the treatment of RNA virus infections.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard-MIT Program in Health Sciences and Technology
Massachusetts Institute of Technology. Computational and Systems Biology Program
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.virol.2016.04.020
