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

doi:10.1016/j.antiviral.2017.03.016

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

Antiviral Res. 2017 Jun:142:136-140. doi: 10.1016/j.antiviral.2017.03.016. Epub 2017 Mar 23.

Authors

Affiliations

¹ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: daiutol@upmc.edu.
² Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
³ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Chemistry and Departments of Biological Sciences, University of Pittsburgh, PA, USA.
⁴ Department of Chemistry and Chemical-Biology, McMaster University, Canada.
⁵ Department of Infectious Diseases and Microbiology, University of Pittsburgh, USA.
⁶ Drug Discovery Institute, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Division of Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Molecular Genetics & Biochemistry, University of Pittsburgh, Pittsburgh, PA, USA.
⁹ Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, USA.
¹⁰ Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, USA.

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.

MeSH terms

Acyclovir / toxicity
Animals
Antiviral Agents / toxicity*
Central Nervous System / drug effects
Chlorocebus aethiops
Drug Evaluation, Preclinical*
Drug Resistance, Viral / drug effects
Herpes Simplex / drug therapy*
Herpes Simplex / virology
Herpesvirus 1, Human / drug effects*
Humans
Immunocompromised Host / drug effects*
Induced Pluripotent Stem Cells / drug effects
Neurons / drug effects
Pluripotent Stem Cells / drug effects
Vero Cells / drug effects

Substances

Antiviral Agents
Acyclovir

Abstract

MeSH terms

Substances

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