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Updated: May 31, 2026
Recurrent Herpetic Stromal Keratitis in Mice, a Model for Studying Human HSK
Published on: December 18, 2012
CK2 inhibitors increase the sensitivity of HSV-1 to interferon-β
Miles C Smith1, Adam M Bayless, Erica T Goddard
1Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045, USA.
Abstract:
Herpes simplex virus type 1 (HSV-1) requires the activities of cellular kinases for efficient replication. The host kinase, CK2, has been shown or is predicted to modify several HSV-1 proteins and has been proposed to affect one or more steps in the viral life cycle. Furthermore, potential cellular and viral substrates of CK2 are involved in antiviral pathways and viral counter-defenses, respectively, suggesting that CK2 regulates these processes. Consequently, we tested whether pharmacological inhibitors of CK2 impaired HSV-1 replication, either alone or in combination with the cellular antiviral factor, interferon-β (IFN-β). Our results indicate that the use of CK2 inhibitors results in a minor reduction in HSV-1 replication but enhanced the inhibitory effect of IFN-β on replication. This effect was dependent on the HSV-1 E3 ubiquitin ligase, infected cell protein 0 (ICP0), which impairs several host antiviral responses, including that produced by IFN-β. Inhibitors of CK2 did not, however, impede the ability of ICP0 to induce the degradation of two cellular targets: the promyelocytic leukemia protein (PML) and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Notably, this effect was only apparent for HSV-1, as the CK2 inhibitors did not enhance the antiviral effect of IFN-β on either vesicular stomatitis virus or adenovirus type 5. Thus, our data suggest that the activity of CK2 is required for an early function during viral infection that assists the growth of HSV-1 in IFN-β-treated cells.
Insights
CK2 inhibitors slightly reduce herpes simplex virus type 1 (HSV-1) replication but boost interferon-β (IFN-β) antiviral activity. This effect relies on HSV-1
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Herpes simplex virus type 1 (HSV-1) replication depends on host cell kinases.
- The host kinase CK2 is implicated in modifying HSV-1 proteins and regulating antiviral pathways.
- CK2's role in HSV-1 infection, particularly alongside interferon-β (IFN-β), requires further investigation.
Purpose of the Study:
- To investigate the impact of CK2 inhibitors on HSV-1 replication.
- To determine if CK2 inhibitors enhance the antiviral effects of IFN-β against HSV-1.
- To elucidate the role of the HSV-1 protein ICP0 in this interaction.
Main Methods:
- Pharmacological inhibition of CK2 activity in HSV-1 infected cells.
- Combination treatment with CK2 inhibitors and IFN-β.
- Assessment of viral replication rates.
- Analysis of viral protein ICP0's effect on cellular targets PML and DNA-PKcs.
Main Results:
- CK2 inhibitors caused a minor reduction in HSV-1 replication.
- CK2 inhibitors significantly enhanced the antiviral effect of IFN-β on HSV-1.
- The enhanced antiviral effect was dependent on the HSV-1 E3 ubiquitin ligase ICP0.
- CK2 inhibitors did not affect ICP0's degradation of PML and DNA-PKcs.
- This synergistic effect was specific to HSV-1, not observed with other viruses.
Conclusions:
- CK2 activity is crucial for an early step in HSV-1 infection that supports viral growth in the presence of IFN-β.
- CK2 inhibitors can potentiate IFN-β-mediated antiviral responses against HSV-1.
- The interaction is specific to HSV-1 and involves the ICP0 protein.
- Targeting CK2 may offer a strategy to enhance antiviral therapies for HSV-1 infections.
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