ArticleProceedings of the National Academy of Sciences of the United States of America2013
Human cytomegalovirus tegument protein pp150 acts as a cyclin A2-CDK-dependent sensor of the host cell cycle and differentiation state.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29 citing papers in PubMed, 38 citations in OpenAlex.
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- Functional and Structural Determinants of Long- and Short-Term Evolution of Herpesvirus Proteins.Molecular biology and evolution · 2025Article
- GraphVelo allows for accurate inference of multimodal velocities and molecular mechanisms for single cells.Nature communications · 2025Article
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- Spatially resolved protein map of intact human cytomegalovirus virions.Nature microbiology · 2023Article
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- Functional single-cell genomics of human cytomegalovirus infection.Nature biotechnology · 2022Article
- Virus-host protein interactions as footprints of human cytomegalovirus replication.Current opinion in virology · 2022Review
- Emerging Mechanisms of GmBio · 2021Review
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- Human Cytomegalovirus UL48 Deubiquitinase Primarily Targets Innermost Tegument Proteins pp150 and Itself To Regulate Their Stability and Protects Virions from Inclusion of Ubiquitin Conjugates.Journal of virology · 2021Article
- The Ins and Outs of Herpesviral Capsids: Divergent Structures and Assembly Mechanisms across the Three Subfamilies.Viruses · 2021Review
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- A molecular mechanism for probabilistic bet hedging and its role in viral latency.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Human cytomegalovirus overcomes SAMHD1 restriction in macrophages via pUL97.Nature microbiology · 2019Article
- Atomic structure of the human herpesvirus 6B capsid and capsid-associated tegument complexes.Nature communications · 2019Article
- Human cytomegalovirus phosphoproteins are hypophosphorylated and intrinsically disordered.The Journal of general virology · 2017Article
- Synthetic lethal mutations in the cyclin A interface of human cytomegalovirus.PLoS pathogens · 2017Article
- Deficiencies in Cellular Processes Modulated by the Retinoblastoma Protein Do Not Account for Reduced Human Cytomegalovirus Replication in Its Absence.Journal of virology · 2015Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Upon cell entry, herpesviruses deliver a multitude of premade virion proteins to their hosts. The interplay between these incoming proteins and cell-specific regulatory factors dictates the outcome of infections at the cellular level. Here, we report a unique type of virion-host cell interaction that is essential for the cell cycle and differentiation state-dependent onset of human cytomegalovirus (HCMV) lytic gene expression. The major tegument 150-kDa phosphoprotein (pp150) of HCMV binds to cyclin A2 via a functional RXL/Cy motif resulting in its cyclin A2-dependent phosphorylation. Alanine substitution of the RXL/Cy motif prevents this interaction and allows the virus to fully escape the cyclin-dependent kinase (CDK)-mediated block of immediate early (IE) gene expression in S/G2 phase that normally restricts the onset of the HCMV replication cycle to G0/G1. Furthermore, the cyclin A2-CDK-pp150 axis is also involved in the establishment of HCMV quiescence in NTera2 cells, showing the importance of this molecular switch for differentiation state-dependent regulation of IE gene expression. Consistent with the known nucleocapsid-binding function of pp150, its RXL/Cy-dependent phosphorylation affects gene expression of the parental virion only, suggesting a cis-acting, virus particle-associated mechanism of control. The pp150 homologs of other primate and mammalian CMVs lack an RXL/Cy motif and accordingly even the nearest relative of HCMV, chimpanzee CMV, starts its lytic cycle in a cell cycle-independent manner. Thus, HCMV has evolved a molecular sensor for cyclin A2-CDK activity to restrict its IE gene expression program as a unique level of self-limitation and adaptation to its human host.
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