The Interactive Complex between Cytomegalovirus Kinase vCDK/pUL97 and Host Factors CDK7-Cyclin H Determines Individual Patterns of Transcription in Infected Cells.

Schütz M, Cordsmeier A, Wangen C, Horn A, Wyler E, Enßer A, Sticht H, Marschall M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 24

Journal Issue: 24

DOI: 10.3390/ijms242417421

Abstract

The infection of human cytomegalovirus (HCMV) is strongly determined by the host-cell interaction in a way that the efficiency of HCMV lytic replication is dependent on the regulatory interplay between viral and cellular proteins. In particular, the activities of protein kinases, 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 vCDK/pUL97, human cyclin H, and CDK7. Major hallmarks of this interplay are the interaction between cyclin H and vCDK/pUL97, which is consistently detectable across various conditions and host cell types of infection, the decrease or increase in pUL97 kinase activity resulting from cyclin H knock-down or elevated levels, respectively, and significant trans-stimulation of human CDK7 activity by pUL97 in vitro. Due to the fact that even a ternary complex of vCDK/pUL97-cyclin H-CDK7 can be detected by coimmunoprecipitation and visualized by bioinformatic structural modeling, we postulated a putative impact of the respective kinase activities on the patterns of transcription in HCMV-infected cells. Here, we undertook a first vCDK/pUL97-specific transcriptomic analysis, which combined conditions of fully lytic HCMV replication with those under specific vCDK/pUL97 or CDK7 drug-mediated inhibition or transient cyclin H knockout. The novel results were further strengthened using bioinformatic modeling of the involved multi-protein complexes. Our data underline the importance of these kinase activities for the C-terminal domain (CTD) phosphorylation-driven activation of host RNA polymerase in HCMV-infected cells. The impact of the individual experimental conditions on differentially expressed gene profiles is described in detail and discussed.

Authors with CRIS profile

Martin Schütz Institute of Clinical and Molecular Virology Arne Cordsmeier Institute of Clinical and Molecular Virology Anselm Horn Professur für Bioinformatik Armin Enßer Institute of Clinical and Molecular Virology Heinrich Sticht Professur für Bioinformatik Manfred Marschall Lehrstuhl für Klinische und Molekulare Virologie

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

None - None A088: Regulatory interaction btw. cyclins and cytomegalovirus kinase pUL97: focus on pUL97 drug resistance mutations Feb. 1, 2020 - July 31, 2023

Involved external institutions

Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE)

How to cite

APA:

Schütz, M., Cordsmeier, A., Wangen, C., Horn, A., Wyler, E., Enßer, A.,... Marschall, M. (2023). The Interactive Complex between Cytomegalovirus Kinase vCDK/pUL97 and Host Factors CDK7-Cyclin H Determines Individual Patterns of Transcription in Infected Cells. International Journal of Molecular Sciences, 24(24). https://doi.org/10.3390/ijms242417421

MLA:

Schütz, Martin, et al. "The Interactive Complex between Cytomegalovirus Kinase vCDK/pUL97 and Host Factors CDK7-Cyclin H Determines Individual Patterns of Transcription in Infected Cells." International Journal of Molecular Sciences 24.24 (2023).

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