The complex between cytomegalovirus pUL97 and host CDK7-cyclin H determines transcription patterns in infected cells
The infection of human cytomegalovirus (HCMV) is determined in its efficiency of productive viral replication through the regulatory interplay between viral and cellular proteins. In particular, protein kinase activities, such as cyclin-dependent kinases (CDKs) and the viral CDK ortholog (vCDK, pUL97) play an important role in both viral reproduction and virus-host interaction. Very recently, we reported on the complexes formed between pUL97, human cyclin H and CDK7. Major hallmarks of this interaction are the constantly detectable interaction of cyclin H with pUL97 under various conditions and host cell types of infection, the reduced or increased pUL97 kinase activity as a consequence of cyclin H knock-down or exogenous addition, respectively, and a significant trans-stimulation of human CDK7 activity by pUL97 in vitro. Due to the fact that even a ternary complex of pUL97-cyclin H-CDK7 could be described by coimmunoprecipitation-based biochemical detection as well as bioinformatic structural modeling, we postulated a putative impact of the respective kinase activities on the patterns of transcription in HCMV-infected cells. Here, we provide a first vCDK/pUL97-specific transcriptomics analysis in primary human fibroblasts, which combines conditions of fully lytic HCMV replication with those under specific pUL97 or CDK7 drug-mediated inhibition or transient cyclin H knock-out.