Design stars: how Small DNA Viruses Remodel the Host Nucleus

Jiang, Mengxi; Imperiale, Michael J.

doi:10.2217/fvl.12.38

Cited by 14 publications

(11 citation statements)

References 126 publications

(151 reference statements)

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“…4). In addition, it is well documented that PML-NBs are transformed into track forms by a viral early gene product, E4orf3 (42,43), suggesting a complex and distinct regulation for each component in infected cells.…”

Section: Discussionmentioning

confidence: 99%

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies

Komatsu

Nagata

Wodrich

2016

J Virol

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Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. IMPORTANCEThe immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and/or subsequent viral DNA replication. Here we performed a detailed analyses of the spatiotemporal distribution of incoming adenoviral genome complexes and found, in contrast to the expectation, that an adenoviral DNA replication factor, but not incoming genomes, targets PML-NBs. Thus, our findings may explain why adenoviral genomes could be observed at PML-NBs in earlier reports but argue against a generalized role for PML-NBs in targeting invading viral genomes.

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Section: Discussionmentioning

confidence: 99%

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies

Komatsu

Nagata

Wodrich

2016

J Virol

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“…Furthermore, many DNA viruses activate the DDR, leading to the phosphorylation of histone γH2AX, which is a key mediator of cellular chromatin remodeling and condensation during DNA repair [8][9][10]. In addition, some DNA viruses such as HPV and HAdV encode viral proteins that can manipulate cellular chromatin [70,[73][74][75]. For example, expression of the HAdV core protein VII alone is sufficient to manipulate cellular chromatin [74].…”

Section: What Dictates the Number Of Replication Compartments That Fomentioning

confidence: 99%

“…Furthermore, the ability of the Hendra virus V protein to form liquid hydrogels that may contribute to cellular toxicity was recently demonstrated [93]. However, although it is well established that nuclear-replicating DNA viruses disrupt existing nuclear biomolecular condensates such as PML NBs, Cajal bodies, and nucleoli [14,25,73,94], if and how LLPS influences the compartmentalization and organization of viral processes, including the formation of VRCs, is unknown. It has been hypothesized that the VRCs of DNA viruses might form via LLPS, as these virus-induced structures demonstrate many characteristics of BMCs [69,95].…”

Section: Biophysical Processes In Replication Compartment Formationmentioning

confidence: 99%

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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“…Most DNA viruses replicate in the nucleus because they need nuclear factors to generate new genomes (reviewed in Schmid et al, 2014;Jiang and Imperiale, 2012). DNA viruses entering the cell are transported by dynein motors along microtubules to the MTOC where they are transferred to the nuclear pore complex for disassembly and release of the DNA genome into the nucleus ( Figure 5).…”

Section: The Dna Viruses Generate Replication Compartments In the Nucmentioning

confidence: 99%

Virus Factories and Mini-Organelles Generated for Virus Replication

Wileman

Netherton

Powell

2016

Encyclopedia of Cell Biology

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Design stars: how Small DNA Viruses Remodel the Host Nucleus

Cited by 14 publications

References 126 publications

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies

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

Virus Factories and Mini-Organelles Generated for Virus Replication

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