RICK activates a NF-κB-dependent anti-human cytomegalovirus response

Eickhoff, J. et al. (2004) RICK activates a NF-κB-dependent anti-human cytomegalovirus response. Journal of Biological Chemistry, 279(10), pp. 9642-9652. (doi: 10.1074/jbc.m312893200) (PMID:14670961)

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The adapter kinase receptor interacting protein-like interacting caspase-like apoptosis regulatory protein kinase (RICK, also called RIP2 and CARDIAK) was found to be elevated at both the protein and RNA levels during human cytomegalovirus (HCMV) replication, suggesting either that the virus may require RICK for replication or that RICK is part of an unsuccessful host attempt to inhibit HCMV replication. It is demonstrated here that forced expression of RICK in either a kinase active or inactive form activates nuclear factor (NF)-κB by means of its intermediate domain and potently blocks HCMV replication in human fibroblasts. Importantly, NF-κB activation, which exerted a modestly positive effect on the early phase of infection, clearly had a strongly negative impact during later viral steps. A stable inhibitor of NF-κB (IκB) reverses the RICK inhibitory effect, and activation of NF-κB by IκB kinase β expression is inhibitory to HCMV, demonstrating that NF-κB activation is part of a potent anti-HCMV response. Supernatant transfer experiments identified interferon-β as a downstream component of the RICK inhibitory pathway. RICK expression was found to synergize with HCMV infection in the induction of interferon-β expression. This study identifies an endogenous RICK-activated, NF-κB- and interferon-β-dependent antiviral pathway that is either inhibited or faulty under normal HCMV replication conditions; efforts to bolster this pathway may lead to novel anti-viral approaches.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cotten, Professor Matthew
Authors: Eickhoff, J., Hanke, M., Stein-Gerlach, M., Kiang, T. P., Herzberger, K., Habenberger, P., Müller, S., Klebl, B., Marschall, M., Stamminger, T., and Cotten, M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Journal of Biological Chemistry
Publisher:American Society for Biochemistry and Molecular Biology
ISSN (Online):1083-351X
Published Online:10 December 2003

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