Abstract：
: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.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Hutterer C,Wandinger SK,Wagner S,Müller R,Stamminger T,Zeitträger I,Godl K,Baumgartner R,Strobl S,Marschall Mdoi
10.1016/j.antiviral.2013.04.017subject
Has Abstractpub_date
2013-08-01 00:00:00pages
139-48issue
2eissn
0166-3542issn
1872-9096pii
S0166-3542(13)00116-2journal_volume
99pub_type
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