Abstract
Replication of human cytomegalovirus (HCMV) is characterized by a tight virus-host cell interaction. Cyclin-dependent protein kinases (CDKs) are functionally integrated into viral gene expression and protein modification. The HCMV-encoded protein kinase pUL97 acts as a CDK ortholog showing structural and functional similarities. Recently, we reported an interaction between pUL97 kinase with a subset of host cyclins, in particular with cyclin T1. Here, we describe an interaction of pUL97 at an even higher affinity with cyclin B1. As a striking feature, the interaction between pUL97 and cyclin B1 proved to be strictly dependent on pUL97 activity, as interaction could be abrogated by treatment with pUL97 inhibitors or by inserting mutations into the conserved kinase domain or the nonconserved C-terminus of pUL97, both producing loss of activity. Thus, we postulate that the mechanism of pUL97-cyclin B1 interaction is determined by an active pUL97 kinase domain.
Highlights
The human cytomegalovirus (HCMV), referred to as human herpesvirus 5 (HHV-5), belongs to the β-Herpesvirinae subfamily
We identified an interaction of the HCMV-encoded protein kinase pUL97 with cyclin
In our ongoing analysis (M.M., unpublished data) and in the previous report by Graf et al [45], we noticed that cyclin interaction of pUL97 was not exclusively restricted to cyclin T1, and included further cyclin types, such as B1, A, and others, and that these interactions can be detected in HCMV-infected cells
Summary
The human cytomegalovirus (HCMV), referred to as human herpesvirus 5 (HHV-5), belongs to the β-Herpesvirinae subfamily. HCMV is a ubiquitous human pathogen, which causes severe systemic diseases in immunosuppressed patients and neonates. Due to a high seroprevalence (60%–90%), HCMV is the leading infectious cause of birth defects in developed countries [1]. For the treatment of HCMV infection, all currently approved antiviral drugs, such as ganciclovir, valganciclovir, cidofovir, and foscarnet inhibit viral DNA replication by targeting the viral DNA polymerase pUL54 [2]. Protein kinases are putative targets of new herpesviral drugs due to their important role in the regulation of HCMV replication [3,4,5,6,7,8]
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