Loading...
CK2 Inhibitors Increase the Sensitivity of HSV-1 to Interferon-β
Smith, Miles Christian Bayless, Adam M. Goddard, Erica T. Davido, David J.
Smith, Miles Christian
Bayless, Adam M.
Goddard, Erica T.
Davido, David J.
Citations
Altmetric:
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 lifecycle. 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 promyelocyticleukemia 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.
Description
Date
2012-09-01
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier Masson
Collections
Research Projects
Organizational Units
Journal Issue
Keywords
HSV-1, CK2, IFN, ICP0, Ad5, VSV
Citation
Smith, Miles C., Adam M. Bayless, Erica T. Goddard, and David J. Davido. "CK2 Inhibitors Increase the Sensitivity of HSV-1 to Interferon-β." Antiviral Research 91.3 (2011): 259-66.