Journal
ANTIVIRAL RESEARCH
Volume 99, Issue 2, Pages 139-148Publisher
ELSEVIER
DOI: 10.1016/j.antiviral.2013.04.017
Keywords
Human cytomegalovirus; Host cell kinome; Mass spectrometry-based profiling; Regulatory protein kinases; Kinase inhibitors; Antiviral targets
Categories
Funding
- Bayerische Forschungsstiftung (BFS) [AZ-872-09]
- Deutsche Forschungsgemeinschaft (DFG) [MA 1289/6-1, MA 1289/7-1]
- Wilhelm Sander-Stiftung [2011.085.1]
- FFL scholarship of the University of Erlangen-Nuremberg
Ask authors/readers for more resources
Human cytomegalovirus infection can lead to life-threatening clinical manifestations particularly in the immunocompromised host. Current therapy options face severe limitations leading to a continued search for alternative drug candidates. Viral replication is dependent on a balanced interaction between viral and cellular proteins. Especially protein kinases are important regulators of virus-host interaction indicated by remarkable kinome alterations induced upon HCMV infection. Here we report a novel approach of kinome profiling with an outcome that suggests an important role of specific cellular protein kinases, such as AMPK, ABL2 and Aurora A. Inhibition of AMPK and ABL kinases showed a significant reduction, whereas inhibition of Aurora A kinase led to a slight activation of HCMV replication, as measured in a GFP reporter-based replication assay. Furthermore, analysis of the mode of antiviral action suggested a substantial benefit for the efficiency of viral replication at the immediate early (AMPK) or early-late (ABL) phases of HCMV gene expression. In contrast, inhibition of Aurora A kinase promoted an enhancement of viral early-late gene expression, suggesting a putative role of Aurora A signaling in host defense. Thus, the combined data provide new information on host cell kinases involved in viral replication and uncovered potential targets for future antiviral strategies. (C) 2013 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available