Formation of adenovirus DNA replication compartments and viral DNA accumulation sites by host chromatin regulatory proteins including NPM1

The adenovirus (Ad) genome is believed to be packaged into the virion by forming a chromatin‐like structure. The replicated viral genome is likely to be condensed through binding with viral core proteins before encapsidation. Replicated viral genomes accumulate in the central region of the nucleus, which we termed virus‐induced postreplication (ViPR) body. However, the molecular mechanism by which the nuclear structure is reorganized and its functional significance in virus production are currently not understood. In this study, we found that viral packaging protein IVa2, but not capsid proteins, accumulated in the ViPR body. In addition, nucleolar chromatin regulatory proteins, nucleophosmin 1 (NPM1), upstream binding factor, and nucleolin accumulated in the ViPR body in late‐stage Ad infection. NPM1 depletion increased the nuclease‐resistant viral genome and delayed the ViPR body formation. These results suggested that structural changes in the infected cell nucleus depend on the formation of viral chromatin by host chromatin regulatory proteins. Because NPM1 depletion decreases production of the infectious virion, we propose that host factor‐mediated viral chromatin remodeling and concomitant ViPR body formation are prerequisites for efficient encapsidation of Ad chromatin.

• Publication year

  2020

• Venue

  The FEBS Journal

• Publication date

  2020-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/febs.15027PMID 31365788
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Self-interaction of NPM1 modulates multiple mechanisms of liquid–liquid phase separation

  2018cited by this paper
• In Vivo Labelling of Adenovirus DNA Identifies Chromatin Anchoring and Biphasic Genome Replication

  2018cited by this paper
• Localization of adenovirus morphogenesis players, together with visualization of assembly intermediates and failed products, favor a model where assembly and packaging occur concurrently at the periphery of the replication center

  2017cited by this paper
• Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine

  2017cited by this paper
• Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA

  2016cited by this paper
• Tracking adenovirus genomes identifies morphologically distinct late DNA replication compartments

  2016cited by this paper
• Structures of Adenovirus Incomplete Particles Clarify Capsid Architecture and Show Maturation Changes of Packaging Protein L1 52/55k

  2015cited by this paper
• Adenoviral L4 33K forms ring-like oligomers and stimulates ATPase activity of IVa2: implications in viral genome packaging

  2015cited by this paper
• Involvement of nucleophosmin (NPM1/B23) in assembly of infectious HPV16 capsids

  2015cited by this paper
• Interaction between nucleophosmin and HBV core protein increases HBV capsid assembly

  2014cited by this paper
• The Amphipathic Helix of Adenovirus Capsid Protein VI Contributes to Penton Release and Postentry Sorting

  2014cited by this paper
• Processing of the L1 52/55k Protein by the Adenovirus Protease: a New Substrate and New Insights into Virion Maturation

  2013cited by this paper
• Intrinsically disordered regions of nucleophosmin/B23 regulate its RNA binding activity through their inter- and intra-molecular association

  2013cited by this paper
• The Adenovirus L4-22K Protein Is Multifunctional and Is an Integral Component of Crucial Aspects of Infection

  2012cited by this paper
• Adenoviral protein V promotes a process of viral assembly through nucleophosmin 1.

  2012cited by this paper
• B23/nucleophosmin is involved in regulation of adenovirus chromatin structure at late infection stages, but not in virus replication and transcription.

  2012cited by this paper
• Presence of the Adenovirus IVa2 Protein at a Single Vertex of the Mature Virion

  2008cited by this paper
• Nucleolar protein B23 has molecular chaperone activities

  2008cited by this paper
• Role for the L1-52/55K Protein in the Serotype Specificity of Adenovirus DNA Packaging

  2008cited by this paper
• Physical and functional interaction between a nucleolar protein nucleophosmin/B23 and adenovirus basic core proteins

  2007cited by this paper
• Relationship between adenovirus DNA replication proteins and nucleolar proteins B23.1 and B23.2

  2007cited by this paper
• Short Communication Relationship between adenovirus DNA replication proteins and nucleolar proteins B23.1 and B23.2

  2007cited by this paper
• Involvement of Template-Activating Factor I/SET in Transcription of Adenovirus Early Genes as a Positive-Acting Factor

  2006cited by this paper
• Nucleolar protein upstream binding factor is sequestered into adenovirus DNA replication centres during infection without affecting RNA polymerase I location or ablating rRNA synthesis

  2006cited by this paper
• Nucleolin is a histone chaperone with FACT‐like activity and assists remodeling of nucleosomes

  2006cited by this paper
• Adenovirus protein IX: a new look at an old protein.

  2005cited by this paper
• Analysis of the Interaction of the Adenovirus L1 52/55-Kilodalton and IVa2 Proteins with the Packaging Sequence In Vivo and In Vitro

  2005cited by this paper
• Functional Interaction of the Adenovirus IVa2 Protein with Adenovirus Type 5 Packaging Sequences

  2005cited by this paper
• Tumor suppressor ARF degrades B23, a nucleolar protein involved in ribosome biogenesis and cell proliferation.

  2003cited by this paper
• The RNA binding activity of a ribosome biogenesis factor, nucleophosmin/B23, is modulated by phosphorylation with a cell cycle-dependent kinase and by association with its subtype.

  2002cited by this paper
• Function of nucleophosmin/B23, a nucleolar acidic protein, as a histone chaperone

  2001cited by this paper
• Adenovirus Protein V Induces Redistribution of Nucleolin and B23 from Nucleolus to Cytoplasm

  2001cited by this paper
• Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication.

  2000cited by this paper
• The ribonuclease activity of nucleolar protein B23.

  1995cited by this paper
• Adenovirus replication and transcription sites are spatially separated in the nucleus of infected cells.

  1994cited by this paper
• Physical mapping of two temperature-sensitive adenovirus mutants affected in the DNA polymerase and DNA binding protein

  1990cited by this paper
• Interaction of nucleolar phosphoprotein B23 with nucleic acids.

  1989cited by this paper
• The structure of adenovirus chromatin in infected cells.

  1985cited by this paper
• Interactions among the three adenovirus core proteins

  1985cited by this paper
• Molecular composition of the adenovirus type 2 virion

  1985cited by this paper
• Detection, rescue, and mapping of mutations in the adenovirus DNA binding protein gene.

  1983cited by this paper
• Adenovirus chromatin structure at different stages of infection

  1981cited by this paper
• Structural proteins of adenoviruses. X. Isolation and topography of low molecular weight antigens from the virion of adenovirus type 2.

  1973cited by this paper

• AML Disparities Across Racial Ancestry Groups: A Spotlight on the NPM1 Mutations

  2026cites this paper
• The cGAS-STING pathway and mitochondrial metabolism: from mechanistic insights to therapeutic potential in tumor

  2026cites this paper
• Bridging innate and adaptive tumor immunity: cGAS–STING pathway activation to potentiate immune checkpoint blockade

  2025cites this paper
• Demystifying the cGAS-STING pathway: precision regulation in the tumor immune microenvironment

  2025cites this paper
• Clicking viruses—with chemistry toward mechanisms in infection

  2025cites this paper
• Mysteries of adenovirus packaging

  2025cites this paper
• The cGAS‒STING pathway in cancer immunity: mechanisms, challenges, and therapeutic implications

  2025cites this paper
• Nucleolin a Central Player in Host Virus Interactions and its Role in Viral Progeny Production

  2025cites this paper
• Targeting cGAS-STING: modulating the immune landscape of hepatic diseases

  2025cites this paper
• Recent advances in targeting the cGAS–STING pathway for immunotherapy in orthopedic diseases

  2025cites this paper
• The adenovirus DNA-binding protein DBP

  2024cites this paper
• Nanoengineering Calcium Peroxide‐Based Site‐Specific Delivery Platform to Efficiently Activate the cGAS‐STING Pathway for Cancer Immunotherapy by Amplified Endoplasmic Reticulum Stress

  2024cites this paper
• cGAS‐STING pathway agonists are promising vaccine adjuvants

  2024cites this paper
• Porcine circovirus type 2 infection promotes the SUMOylation of nucleophosmin-1 to facilitate the viral circular single-stranded DNA replication

  2024cites this paper
• Controlling Much? Viral Control of Host Chromatin Dynamics.

  2024cites this paper
• Nuclear reorganization by NPM1-mediated phase separation triggered by adenovirus core protein VII

  2024influential citation
• The protein composition of human adenovirus replication compartments

  2024cites this paper
• Adenoviral chromatin organization primes for early gene activation

  2023cites this paper
• Changes in adenoviral chromatin organization precede early gene activation upon infection

  2023cites this paper
• Nucleophosmin 1a translocated from nucleus to cytoplasm and facilitate GCRV replication.

  2023cites this paper
• Activation of Stimulation of Interferon Genes (STING) Signal and Cancer Immunotherapy

  2022cites this paper
• Novel viral splicing events and open reading frames revealed by long-read direct RNA sequencing of adenovirus transcripts

  2022cites this paper
• Replication Compartments of Eukaryotic and Bacterial DNA Viruses: Common Themes Between Different Domains of Host Cells

  2022cites this paper
• Manipulation of Cellular Processes via Nucleolus Hijaking in the Course of Viral Infection in Mammals

  2021cites this paper
• DNA-PK phosphorylation at Ser2056 during adenovirus E4 mutant infection is promoted by viral DNA replication and independent of the MRN complex.

  2021cites this paper
• Mutual dependency between lncRNA LETN and protein NPM1 in controlling the nucleolar structure and functions sustaining cell proliferation

  2021cites this paper
• cGAS-STING pathway in cancer biotherapy

  2020cites this paper
• Fluorescent protein tagging of adenoviral proteins pV and pIX reveals ‘late virion accumulation compartment’

  2020cites this paper
• Lytic Reactivation of the Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) Is Accompanied by Major Nucleolar Alterations

  2020cites this paper
• Murine polyomavirus DNA transitions through spatially distinct nuclear replication subdomains during infection

  2020cites this paper
• Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

  2020cites this paper
• Viral and cellular interactions during adenovirus DNA replication

  2019cites this paper
• Imaging the adenovirus infection cycle

  2019cites this paper