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Cited by 43Cytomegalovirus and herpesvirus researchHerpesvirus Infections and TreatmentsViral-associated cancers and disorders

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Profiling of the kinome of cytomegalovirus-infected cells reveals the functional importance of host kinases Aurora A, ABL and AMPK

Hutterer, Corina, Wandinger, Sebastian Karl, Wagner, Sabrina, Müller, Regina, Stamminger, Thomas, Zeitträger, Isabel, Godl, Klaus, Baumgartner, Roland, Strobl, Stefan, Marschall, Manfred·2013·Antiviral Research
DOI 10.1016/j.antiviral.2013.04.017
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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.

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Metadata

Authors
Hutterer, C., Wandinger, S. K., Wagner, S., Müller, R., Stamminger, T., Zeitträger, I., Godl, K., Baumgartner, R., Strobl, S., & Marschall, M.
Affiliations
  • Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
  • Evotec (Germany) (DE)
  • 4SC (Germany) (DE)
Corresponding author
Hutterer, Corina
ORCID
Venue
Antiviral Research
Publisher
Elsevier BV
Published
2013-08
Volume
99
Issue
2
Pages
139-148
ISSN
0166-3542 (ISSN-L)
DOI
10.1016/j.antiviral.2013.04.017
OpenAlex
W2077185287
Cited by
43
References
3
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 2 · 2013: 3
FWCI
3.41
Type
journal article
Language
en
Open access
closed
Locations
  • Antiviral Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
  • Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
Keywords
human cytomegalovirus, kinome profiling, AURKA, AMPK, host-virus interaction, viral replication, antiviral drug targets, kinase inhibition, immunocompromised patients
MeSH terms
Imatinib Mesylate, Serine-Threonine Kinase 3, Hippo Kinases, Antiviral Agents, Benzamides, Cells, Cultured, Cytomegalovirus Infections, Cytomegalovirus, Humans, Piperazines, Pyrimidines, Virus Replication, Gene Expression Regulation, Viral, Proto-Oncogene Proteins c-abl, Protein Serine-Threonine Kinases, Nucleic Acid Synthesis Inhibitors, Protein Kinase Inhibitors, Intracellular Signaling Peptides and Proteins, Cell Proliferation, AMP-Activated Protein Kinases, Aurora Kinase A

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