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.
N1 - Funding Information:
This project was funded from NIH grants 5R01MH063480-12 and 5R01MH045817; Scioto Foundation grant07R-1712; and Pittsburgh Center for Kidney Research Kidney Imaging Core NIH P30 DK079307.
Publisher Copyright:
© 2017 Elsevier B.V.
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.
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U2 - 10.1016/j.antiviral.2017.03.016
DO - 10.1016/j.antiviral.2017.03.016
M3 - Article
C2 - 28342892
AN - SCOPUS:85016388870
SN - 0166-3542
VL - 142
SP - 136
EP - 140
JO - Antiviral Research
JF - Antiviral Research
ER -