Related Experiment Video
Updated: Jan 19, 2026
Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells
Published on: September 14, 2016
Cellular Signaling Analysis shows antiviral, ribavirin-mediated ribosomal signaling modulation
Xianting Ding1, Peter O Krutzik2, Amir Ali Ghaffari3
1Institute for Personalized Medicine, State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
Abstract:
As antiviral drug resistance develops and new viruses emerge there is a pressing need to develop strategies to rapidly develop antiviral therapeutics. Here we use phospho-specific flow cytometry to assess perturbations of many different cellular signaling pathways during treatment with drug combinations that are highly effective in blocking Herpes simplex virus type 1 (HSV-1) infection. We discovered two antiviral drug combinations act on distinct signaling pathways, either STAT1 or S6 phosphorylation, to block HSV-1 infection. We focused on upregulation of S6 phosphorylation by HSV-1 infection, and our subsequent finding that ribavirin antagonizes this upregulation of S6 phosphorylation. We go on to show that the S6 kinase inhibitor SL0101 blocks HSV-1 replication in vitro and in an in vivo animal model of HSV-1 infection. Overall, we have used an unbiased analysis of cellular signaling pathways during treatment by antiviral drug combinations to discover a novel antiviral drug target against HSV-1 infection. The outcomes of the approach we present highlight the importance of analyzing how antiviral drugs modulate cellular and pathogen-induced signaling as a method to discover new drug therapy targets.
Insights
Researchers identified novel antiviral strategies targeting cellular signaling pathways to combat Herpes simplex virus type 1 (HSV-1) infection. Targeting S6 phosphorylation with the inhibitor SL0101 effectively blocks viral replication in vitro and in vivo.
Area of Science:
- Virology
- Immunology
- Drug Discovery
Background:
- Antiviral drug resistance and emerging viruses necessitate rapid development of new therapeutics.
- Herpes simplex virus type 1 (HSV-1) remains a significant public health concern requiring effective treatment strategies.
Purpose of the Study:
- To identify novel antiviral drug targets by analyzing cellular signaling pathway perturbations during HSV-1 infection.
- To investigate the role of S6 phosphorylation in HSV-1 replication and its modulation by antiviral drugs.
Main Methods:
- Phospho-specific flow cytometry was employed to assess cellular signaling pathway activity.
- Drug combinations effective against HSV-1 were analyzed for their impact on host cell signaling.
- The efficacy of an S6 kinase inhibitor (SL0101) was evaluated in vitro and in an animal model.
Main Results:
- Two antiviral drug combinations were found to inhibit HSV-1 by targeting distinct pathways: STAT1 or S6 phosphorylation.
- HSV-1 infection upregulates S6 phosphorylation, which is antagonized by ribavirin.
- The S6 kinase inhibitor SL0101 demonstrated efficacy in blocking HSV-1 replication both in vitro and in vivo.
Conclusions:
- Unbiased analysis of cellular signaling pathways reveals novel therapeutic targets for HSV-1.
- Targeting S6 phosphorylation represents a promising strategy for developing new antiviral therapies against HSV-1.
- Understanding drug-modulated signaling pathways is crucial for discovering effective antiviral treatments.
Related Concept Videos
01:21Paracrine Signaling
08:24Imaging G Protein-coupled Receptor-mediated Chemotaxis and its Signaling Events in Neutrophil-like HL60 Cells
09:47DeepOmicsAE: Representing Signaling Modules in Alzheimer's Disease with Deep Learning Analysis of Proteomics, Metabolomics, and Clinical Data
10:03Rapid and Robust Analysis of Cellular and Molecular Polarization Induced by Chemokine Signaling
02:29Modulating Sensory Neuronal Signaling in a Mouse Model Using Near Infrared Light
02:03What is Cell Signaling?