Comparison of three cell-based drug screening platforms for HSV-1 infection

Leonardo D'Aiuto, Kelly Williamson, Peter Dimitrion, James McNulty, Carla E. Brown, Chanti Babu Dokuburra, Alexander J. Nielsen, Wen Jing Lin, Paolo Piazza, Mark E. Schurdak, Joel Wood, Robert H Yolken, Paul R. Kinchington, David C. Bloom, Vishwajit L. Nimgaonkar

Research output: Contribution to journalArticle

Abstract

Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

Original languageEnglish (US)
Pages (from-to)136-140
Number of pages5
JournalAntiviral Research
Volume142
DOIs
StatePublished - Jun 1 2017

Fingerprint

Preclinical Drug Evaluations
Human Herpesvirus 1
Virus Diseases
Induced Pluripotent Stem Cells
Acyclovir
Pharmaceutical Preparations
Antiviral Agents
Vero Cells
Neurons
Stem Cells
Immunocompromised Host
Encephalitis
Infection
Haplorhini
Central Nervous System
Epithelial Cells
Viruses
Cell Line

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

D'Aiuto, L., Williamson, K., Dimitrion, P., McNulty, J., Brown, C. E., Dokuburra, C. B., ... Nimgaonkar, V. L. (2017). Comparison of three cell-based drug screening platforms for HSV-1 infection. Antiviral Research, 142, 136-140. https://doi.org/10.1016/j.antiviral.2017.03.016

Comparison of three cell-based drug screening platforms for HSV-1 infection. / D'Aiuto, Leonardo; Williamson, Kelly; Dimitrion, Peter; McNulty, James; Brown, Carla E.; Dokuburra, Chanti Babu; Nielsen, Alexander J.; Lin, Wen Jing; Piazza, Paolo; Schurdak, Mark E.; Wood, Joel; Yolken, Robert H; Kinchington, Paul R.; Bloom, David C.; Nimgaonkar, Vishwajit L.

In: Antiviral Research, Vol. 142, 01.06.2017, p. 136-140.

Research output: Contribution to journalArticle

D'Aiuto, L, Williamson, K, Dimitrion, P, McNulty, J, Brown, CE, Dokuburra, CB, Nielsen, AJ, Lin, WJ, Piazza, P, Schurdak, ME, Wood, J, Yolken, RH, Kinchington, PR, Bloom, DC & Nimgaonkar, VL 2017, 'Comparison of three cell-based drug screening platforms for HSV-1 infection', Antiviral Research, vol. 142, pp. 136-140. https://doi.org/10.1016/j.antiviral.2017.03.016
D'Aiuto L, Williamson K, Dimitrion P, McNulty J, Brown CE, Dokuburra CB et al. Comparison of three cell-based drug screening platforms for HSV-1 infection. Antiviral Research. 2017 Jun 1;142:136-140. https://doi.org/10.1016/j.antiviral.2017.03.016
D'Aiuto, Leonardo ; Williamson, Kelly ; Dimitrion, Peter ; McNulty, James ; Brown, Carla E. ; Dokuburra, Chanti Babu ; Nielsen, Alexander J. ; Lin, Wen Jing ; Piazza, Paolo ; Schurdak, Mark E. ; Wood, Joel ; Yolken, Robert H ; Kinchington, Paul R. ; Bloom, David C. ; Nimgaonkar, Vishwajit L. / Comparison of three cell-based drug screening platforms for HSV-1 infection. In: Antiviral Research. 2017 ; Vol. 142. pp. 136-140.
@article{de4c0fb5b3e24cd2bd6389660e8556ea,
title = "Comparison of three cell-based drug screening platforms for HSV-1 infection",
abstract = "Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.",
author = "Leonardo D'Aiuto and Kelly Williamson and Peter Dimitrion and James McNulty and Brown, {Carla E.} and Dokuburra, {Chanti Babu} and Nielsen, {Alexander J.} and Lin, {Wen Jing} and Paolo Piazza and Schurdak, {Mark E.} and Joel Wood and Yolken, {Robert H} and Kinchington, {Paul R.} and Bloom, {David C.} and Nimgaonkar, {Vishwajit L.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.antiviral.2017.03.016",
language = "English (US)",
volume = "142",
pages = "136--140",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",

}

TY - JOUR

T1 - Comparison of three cell-based drug screening platforms for HSV-1 infection

AU - D'Aiuto, Leonardo

AU - Williamson, Kelly

AU - Dimitrion, Peter

AU - McNulty, James

AU - Brown, Carla E.

AU - Dokuburra, Chanti Babu

AU - Nielsen, Alexander J.

AU - Lin, Wen Jing

AU - Piazza, Paolo

AU - Schurdak, Mark E.

AU - Wood, Joel

AU - Yolken, Robert H

AU - Kinchington, Paul R.

AU - Bloom, David C.

AU - Nimgaonkar, Vishwajit L.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

AB - Acyclovir (ACV) and its derivatives have been highly effective for treating recurrent, lytic infections with Herpes Simplex Virus, type 1 (HSV-1), but searches for additional antiviral drugs are motivated by recent reports of resistance to ACV, particularly among immunocompromised patients. In addition, the relative neurotoxicity of ACV and its inability to prevent neurological sequelae among HSV-1 encephalitis survivors compel searches for new drugs to treat HSV-1 infections of the central nervous system (CNS). Primary drug screens for neurotropic viruses like HSV-1 typically utilize non-neuronal cell lines, but they may miss drugs that have neuron specific antiviral effects. Therefore, we compared the effects of a panel of conventional and novel anti-herpetic compounds in monkey epithelial (Vero) cells, human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and hiPSC-derived neurons (N = 73 drugs). While the profiles of activity for the majority of the drugs were similar in all three tissues, Vero cells were less likely than NPCs to identify drugs with substantial inhibitory activity in hiPSC-derived neurons. We discuss the relative merits of each cell type for antiviral drug screens against neuronal infections with HSV-1.

UR - http://www.scopus.com/inward/record.url?scp=85016388870&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016388870&partnerID=8YFLogxK

U2 - 10.1016/j.antiviral.2017.03.016

DO - 10.1016/j.antiviral.2017.03.016

M3 - Article

C2 - 28342892

AN - SCOPUS:85016388870

VL - 142

SP - 136

EP - 140

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

ER -