Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies

Vyas Ramanan; Kartik Trehan; Mei-Lyn Ong; Joseph M Luna; Hans-Heinrich Hoffmann; Christine Espiritu; Timothy P Sheahan; Hamsika Chandrasekar; Robert E Schwartz; Kathleen S Christine; Charles M Rice; Alexander van Oudenaarden; Sangeeta N Bhatia

doi:10.1016/j.virol.2016.04.020

Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies

Vyas Ramanan, Kartik Trehan, Mei-Lyn Ong, Joseph M Luna, Hans-Heinrich Hoffmann, Christine Espiritu, Timothy P Sheahan, Hamsika Chandrasekar, Robert E Schwartz, Kathleen S Christine, Charles M Rice, Alexander van Oudenaarden, Sangeeta N Bhatia

Hubrecht Institute

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

14 Citaten (Scopus)

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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.

Originele taal-2	Engels
Pagina's (van-tot)	236-47
Aantal pagina's	12
Tijdschrift	Virology
Volume	494
DOI's	https://doi.org/10.1016/j.virol.2016.04.020
Status	Gepubliceerd - jul. 2016

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10.1016/j.virol.2016.04.020

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Ramanan, V., Trehan, K., Ong, M.-L., Luna, J. M., Hoffmann, H.-H., Espiritu, C., Sheahan, T. P., Chandrasekar, H., Schwartz, R. E., Christine, K. S., Rice, C. M., van Oudenaarden, A., & Bhatia, S. N. (2016). Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies. Virology, 494, 236-47. https://doi.org/10.1016/j.virol.2016.04.020

@article{7320e83b035f4ebb81b7c8328f182fe6,

title = "Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies",

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.",

author = "Vyas Ramanan and Kartik Trehan and Mei-Lyn Ong and Luna, {Joseph M} and Hans-Heinrich Hoffmann and Christine Espiritu and Sheahan, {Timothy P} and Hamsika Chandrasekar and Schwartz, {Robert E} and Christine, {Kathleen S} and Rice, {Charles M} and {van Oudenaarden}, Alexander and Bhatia, {Sangeeta N}",

year = "2016",

month = jul,

doi = "10.1016/j.virol.2016.04.020",

language = "English",

volume = "494",

pages = "236--47",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press",

}

Ramanan, V, Trehan, K, Ong, M-L, Luna, JM, Hoffmann, H-H, Espiritu, C, Sheahan, TP, Chandrasekar, H, Schwartz, RE, Christine, KS, Rice, CM, van Oudenaarden, A & Bhatia, SN 2016, 'Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies', Virology, vol. 494, blz. 236-47. https://doi.org/10.1016/j.virol.2016.04.020

TY - JOUR

T1 - Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies

AU - Ramanan, Vyas

AU - Trehan, Kartik

AU - Ong, Mei-Lyn

AU - Luna, Joseph M

AU - Hoffmann, Hans-Heinrich

AU - Espiritu, Christine

AU - Sheahan, Timothy P

AU - Chandrasekar, Hamsika

AU - Schwartz, Robert E

AU - Christine, Kathleen S

AU - Rice, Charles M

AU - van Oudenaarden, Alexander

AU - Bhatia, Sangeeta N

PY - 2016/7

Y1 - 2016/7

N2 - 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.

AB - 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.

U2 - 10.1016/j.virol.2016.04.020

DO - 10.1016/j.virol.2016.04.020

M3 - Article

C2 - 27128351

SN - 0042-6822

VL - 494

SP - 236

EP - 247

JO - Virology

JF - Virology

ER -

Viral genome imaging of hepatitis C virus to probe heterogeneous viral infection and responses to antiviral therapies

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