ArticleJournal of virology2012
Inhibition of human cytomegalovirus immediate-early gene expression by cyclin A2-dependent kinase activity.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 31 citations in OpenAlex.
- A murine cytomegalovirus cell cycle regulator (m54.5p) evolved within the conserved viral DNA polymerase gene.PLoS pathogens · 2026Article
- DUX4-stimulated genes define an antiviral defense program in human placental trophoblasts.The Journal of experimental medicine · 2025Article
- SARS-CoV-2 encoded ORF3a interacts with YY1 to promote latent HCMV reactivation.PLoS pathogens · 2025Article
- The S-Phase Arrest of Host Cells Caused by an Alpha-Herpesvirus Genome Replication Facilitates Viral Recruitment of RNA Polymerase II to Transcribe Viral Genes.Cell proliferation · 2025Article
- Highly Conserved Interaction Profiles between Clinically Relevant Mutants of the Cytomegalovirus CDK-like Kinase pUL97 and Human Cyclins: Functional Significance of Cyclin H.International journal of molecular sciences · 2022Article
- Article
- Emerging Mechanisms of GmBio · 2021Review
- Human Cytomegalovirus RNA2.7 Is Required for Upregulating Multiple Cellular Genes To Promote Cell Motility and Viral Spread Late in Lytic Infection.Journal of virology · 2021Article
- The degree of polymerization and sulfation patterns in heparan sulfate are critical determinants of cytomegalovirus entry into host cells.PLoS pathogens · 2021Article
- Importance of miR-UL-148D Expression Pattern in Cytomegalovirus Infected Transplant Patients.International journal of organ transplantation medicine · 2021Article
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Control of Immediate Early Gene Expression for Human Cytomegalovirus Reactivation.Frontiers in cellular and infection microbiology · 2020Review
- Activation of E2F-dependent transcription by the mouse cytomegalovirus M117 protein affects the viral host range.PLoS pathogens · 2018Article
- The host ubiquitin-dependent segregase VCP/p97 is required for the onset of human cytomegalovirus replication.PLoS pathogens · 2017Article
- Synthetic lethal mutations in the cyclin A interface of human cytomegalovirus.PLoS pathogens · 2017Article
- Human Cytomegalovirus miR-UL148D Facilitates Latent Viral Infection by Targeting Host Cell Immediate Early Response Gene 5.PLoS pathogens · 2016Article
- Article
- Human cytomegalovirus riding the cell cycle.Medical microbiology and immunology · 2015Review
- MicroRNA miR-21 attenuates human cytomegalovirus replication in neural cells by targeting Cdc25a.Journal of virology · 2015Article
- PUL21a-Cyclin A2 interaction is required to protect human cytomegalovirus-infected cells from the deleterious consequences of mitotic entry.PLoS pathogens · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human cytomegalovirus (HCMV) starts its lytic replication cycle only in the G(0)/G(1) phase of the cell division cycle. S/G(2) cells can be infected but block the onset of immediate-early (IE) gene expression. This block can be overcome by inhibition of cyclin-dependent kinases (CDKs), suggesting that cyclin A2, the only cyclin with an S/G(2)-specific activity profile, may act as a negative regulator of viral gene expression. To directly test this hypothesis, we generated derivatives of an HCMV-permissive glioblastoma cell line that express cyclin A2 in a constitutive, cell cycle-independent manner. We demonstrate that even moderate cyclin A2 overexpression in G(1) was sufficient to severely compromise the HCMV replicative cycle after high-multiplicity infection. This negative effect was composed of a strong but transient inhibition of IE gene transcription and a more sustained alteration of IE mRNA processing, resulting in reduced levels of UL37 and IE2, an essential transactivator of viral early gene expression. Consistently, cyclin A2-overexpressing cells showed a strong delay of viral early and late gene expression, as well as virus reproduction. All effects were dependent on CDK activity, as a cyclin A2 mutant deficient in CDK binding was unable to interfere with the HCMV infectious cycle. Interestingly, murine CMV, whose IE gene expression is known to be cell cycle independent, is not affected by cyclin A2. Instead, it upregulates cyclin A2-associated kinase activity upon infection. Understanding the mechanisms behind the HCMV-specific action of cyclin A2-CDK might reveal new targets for antiviral strategies.
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