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

Genoveso, Michelle Jane Clemeno; Hisaoka, Miharu; Komatsu, Tetsuro; Wodrich, Harald; Nagata, Kyosuke; Okuwaki, Mitsuru

doi:10.1111/febs.15027

Cited by 24 publications

(33 citation statements)

References 43 publications

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“…They transition from a discrete rounded morphology to a more broken and diffuse morphology and finally to ring-like assemblies [14]. The morphological changes coincide with the formation of virus-induced post-replicative (ViPR) bodies, which are implicated in adenovirus genome packaging [78,103,176] (see also the following section on virus-induced assemblies proximal to replication compartments). This raises questions as to how changes in VRCs might functionally impact late viral processes such as viral late gene expression, capsid assembly, and genome packaging.…”

Section: Structure Of Replication Centers and Organization Of Viral Pmentioning

confidence: 96%

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Charman

Weitzman

2020

Viruses

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DNA viruses that replicate in the nucleus encompass a range of ubiquitous and clinically important viruses, from acute pathogens to persistent tumor viruses. These viruses must co-opt nuclear processes for the benefit of the virus, whilst evading host processes that would otherwise attenuate viral replication. Accordingly, DNA viruses induce the formation of membraneless assemblies termed viral replication compartments (VRCs). These compartments facilitate the spatial organization of viral processes and regulate virus-host interactions. Here, we review advances in our understanding of VRCs. We cover their initiation and formation, their function as the sites of viral processes, and aspects of their composition and organization. In doing so, we highlight ongoing and emerging areas of research highly pertinent to our understanding of nuclear-replicating DNA viruses.Viruses 2020, 12, 151 2 of 20 The Initiation and Formation of Replication CompartmentsDNA viruses that replicate in the nucleus exhibit a diverse array of strategies to complete their replication cycle and ultimately produce progeny virions. Despite their many differences, the strategies employed by DNA viruses to initiate productive infection and establish VRCs share many features in common. Indeed, it is likely that all DNA viruses that replicate in the nucleus form VRCs. Following penetration of the host cell and the transport of viral capsids/cores, viral DNA genomes enter the nucleus, where they begin a program of temporally regulated gene expression that initiates productive infection [1,2]. Early gene products include viral proteins required to manipulate the host-cell environment and replicate the viral genome. Viral replication proteins interact with the viral genome and initiate genome replication leading to VRC formation, which is often in concert with certain co-opted host proteins. However, these viruses must overcome several challenges to form VRCs successfully. Firstly, incoming genomes must avoid cellular intrinsic antiviral defenses and homeostatic regulatory pathways such as elements of the DNA damage response (DDR) that respond to the presence of foreign DNA and act to suppress viral gene expression [3][4][5][6][7][8][9][10]. Secondly, VRCs typically form at specific sites within the nucleus, suggesting that viral genomes need to be targeted to these sites in order to initiate VRC formation [6,11,12]. Furthermore, it has been hypothesized that the formation and growth of VRCs may require manipulation of the nuclear environment and the re-organization of host chromatin to overcome the spatial restraints of the nucleus [11][12][13][14][15]. In this section, we review key features of VRC initiation and highlight some major challenges to VRC formation. Interplay between Viral Replication Compartment Formation and Promyelocytic Leukemia Protein Nuclear BodiesA common theme amongst many nuclear-replicating DNA viruses is initiation of VRCs at sites in close proximity to promyelocytic leukemia protein (PML) nuclear bodies (NBs). Since the dis...

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Section: Structure Of Replication Centers and Organization Of Viral Pmentioning

confidence: 96%

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Charman

Weitzman

2020

Viruses

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“…Currently, DBP is frequently used as reference stain to describe spatial and temporal events in the nucleus of Ad‐infected cells . In addition, DBP was used to characterize Ad replication itself to identify cellular and viral proteins that are sequestered into viral RCs or used as spatial or timing reference to study non‐RC‐linked events . Recent super‐resolution microscopy performed on isolated replication compartments from infected HeLa cells suggests a dynamic RC subcompartmentalization of DBP .…”

Section: From Genome Import To Particle Egressmentioning

confidence: 99%

Imaging the adenovirus infection cycle

Pied

Wodrich

2019

FEBS Letters

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Edited by Urs GreberIncoming adenoviruses seize control of cytosolic transport mechanisms to relocate their genome from the cell periphery to specialized sites in the nucleoplasm. The nucleus is the site for viral gene expression, genome replication, and the production of progeny for the next round of infection. By taking control of the cell, adenoviruses also suppress cell-autonomous immunity responses. To succeed in their production cycle, adenoviruses rely on wellcoordinated steps, facilitated by interactions between viral proteins and cellular factors. Interactions between virus and host can impose remarkable morphological changes in the infected cell. Imaging adenoviruses has tremendously influenced how we delineate individual steps in the viral life cycle, because it allowed the development of specific optical markers to label these morphological changes in space and time. As technology advances, innovative imaging techniques and novel tools for specimen labeling keep uncovering previously unseen facets of adenovirus biology emphasizing why imaging adenoviruses is as attractive today as it was in the past. This review will summarize past achievements and present developments in adenovirus imaging centered on fluorescence microscopy approaches.Adenoviruses (Ads) are nonenveloped icosahedral viruses with a diameter of~90 nm with slight structural differences between genotypes. The majority of the Ad capsid shell is composed of 240 hexon trimers, and each of the 12 vertices of the icosahedron is occupied by a penton. Pentons are involved in cell attachment and receptor recognition and are composed of the pentameric penton base from which the trimeric fiber molecule extends. Minor capsid proteins IIIa, VI, VIII, and IX are embedded in the capsid and contribute to capsid stability. Protein VI is located at the inner surface of the capsid, and biochemical data suggest that it may connect the capsid to the core containing the viral genome via protein V. The genome is ã 36-kb double-stranded linear DNA molecule with the terminal protein (TP) covalently bound to each 5 0end. Adenovirus genomes are highly condensed and organized into chromatin by several hundred copies of Abbreviations ADP, adenovirus death protein

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“…In addition, it is not known whether the dispersion represents a cellular response to viral infection, or whether it take place due to the formation of replication compartments that generate condensed peripheral chromatin and thus may favor virus replication. Nevertheless, recruitment of particular nucleolar proteins to replication compartments, such as Nucleolin, which was previously reported to participate in the formation of adenovirus and hCMV replication compartments [39,72,73], may indicate a role for these proteins in virus replication and/or assembly. Of note, analysis of the proteome associated with adenovirus and HSV-1 genomes illustrated enrichment of nucleolar proteins, including components of RNA polymerase I and the processome small subunit complex, which were suggested to promote expression of viral genes [48].…”

Section: Discussionmentioning

confidence: 97%

“…It has also been postulated that maintaining the global production of pre-rRNA avoids activation of nucleolar stress, which can lead to cell cycle arrest and apoptosis [85]. In addition, nucleolar proteins may acquire unique functions to promote viral infection as exemplified for Nucleolin, which is recruited to viral replication compartments (RCs) during HSV-1 and human cytomegalovirus (hCMV) infection [39,40,72].…”

Section: Discussionmentioning

confidence: 99%

“…For example, replication and transcription of Borna disease virus take place in the nucleolus [27], assembly of AAV occurs in the nucleolus [28], REV protein of HIV is localized to the nucleolus [29,30], and modifications of the basal rRNA transcription factors, Selectivity Factor-1 (SL-1) and UBF, inhibit the activity of RNA polymerase I during poliovirus infection [31,32]. In addition, NSs protein encoded by Schmallenberg virus of the bunyaviridae family, is targeted to the nucleolus and triggers nucleolar disruption [33], and redistribution of UBF, Nucleolin and NPM1 during adenovirus infection promotes nuclear reorganization, viral DNA replication, and virion assembly [23,[34][35][36][37][38][39]]. An almost complete destruction of the nucleolar structure, involving dispersion of nucleolar proteins, including UBF, Fibrillarin, Nucleolin and NPM1 to distinct cellular sites, has been described following infection with herpes simplex virus type 1 (HSV-1) [40, 41].…”

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Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

Atari

Rajan

Chikne

et al. 2020

Preprint

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The nucleolus is a sub-nuclear compartment whose primary function is the biogenesis of ribosomal subunits. Certain viral infections affect the morphology and composition of the nucleolar compartment and influence ribosomal RNA (rRNA) transcription and maturation. However, no description of nucleolar morphology and function during infection with Kaposi's sarcoma-associated herpesvirus (KSHV) is available to date. Using immunofluorescence microscopy, we documented extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. This was manifested by redistribution of key nucleolar proteins, including the rRNA transcription factor, UBF, the essential pre-rRNA processing factor Fibrillarin, and the nucleolar multifunctional phosphoproteins Nucleophosmin (NPM1) and Nucleolin. Distinct delocalization patterns were evident; certain nucleolar proteins remained together whereas others dissociated, implying that nucleolar proteins undergo nonrandom programmed dispersion. Of note, neither Fibrillarin nor UBF colocalized with promyelocytic leukemia (PML) nuclear bodies or with the viral protein LANA-1, and their redistribution was not dependent on viral DNA replication or late viral gene expression. No significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found by RT-qPCR and Northern blot analysis, respectively. Furthermore, fluorescent in situ hybridization (FISH), combined with immunofluorescence, revealed an overlap between Fibrillarin and internal transcribed spacer 1 (ITS1), which represents the primary product of the pre-rRNA, suggesting that the processing of rRNA proceeds during lytic reactivation. Finally, small changes in the levels of pseudouridylation were documented across the rRNA. Taken together, our results suggest that rRNA transcription and processing persist during lytic reactivation of KSHV, yet they may become uncoupled. Whether the observed nucleolar alterations favor productive infection or signify cellular anti-viral responses remains to be determined. Author SummaryWe describe the extensive destruction of the nuclear and nucleolar architecture during lytic reactivation of KSHV. Distinct delocalization patterns are illustrated: certain nucleolar proteins remained associated with each other whereas others dissociated, implying that nucleolar proteins undergo nonrandom , 3 programmed dispersion. Of note, no significant changes in pre-rRNA levels and no accumulation of pre-rRNA intermediates were found, suggesting that pre-RNA transcription and processing continue and could be uncoupled during lytic reactivation. Small changes in the levels of pseudouridylation were documented across the rRNA. Previous studies showed that the different forms of KSHV infection are controlled through cellular and viral functions, which reprogram host epigenetic, transcriptomic, posttranscriptomic and proteomic landscapes. The ability of KSHV to affect the nucleolus and rRNA modifications constitutes a novel interaction network between viral and cellula...

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

Cited by 24 publications

References 43 publications

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Replication Compartments of DNA Viruses in the Nucleus: Location, Location, Location

Imaging the adenovirus infection cycle

Lytic Reactivation of the Kaposi’s sarcoma-associated herpesvirus (KSHV) is Accompanied by Major Nucleolar Alterations

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