Take your PIKK: tumour viruses and DNA damage response pathways

Pancholi, Neha J.; Price, Alexander M.; Weitzman, Matthew D.

doi:10.1098/rstb.2016.0269

Cited by 39 publications

(32 citation statements)

References 117 publications

(249 reference statements)

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“…Many DNA viruses hijack cellular chromatin modifiers to regulate their own viral chromatin, as well as cellular chromatin [70][71][72]. 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].…”

Section: What Dictates the Number Of Replication Compartments That Fomentioning

confidence: 99%

“…Thus, DDR proteins may be considered common components of VRCs. While some DDR pathways are antagonized by DNA viruses to prevent the DDR from attenuating infection, others are activated by viruses to promote viral processes [8][9][10]124,125]. However, exactly how cellular DNA repair and DNA replication factors are harnessed to promote viral processes is often unclear.…”

Section: The Composition Of Replication Compartmentsmentioning

confidence: 99%

“…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].…”

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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: What Dictates the Number Of Replication Compartments That Fomentioning

confidence: 99%

Section: The Composition Of Replication Compartmentsmentioning

confidence: 99%

mentioning

confidence: 99%

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

Charman

Weitzman

2020

Viruses

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“…Lunn et al [15] provide an overview on the epidemiology of viral tumours, outlining their common characteristics as well as their differences. Technologies have made enormous progress since 1964 and the complex interplay between viruses and their hosts is being uncovered at the molecular level: viral genomics by Tang & Larsson [16]; innate immune evasion by Hopcraft & Damania [17]; and viral regulation of DNA replication and repair by Pancholi et al [18]. The recognition that viruses can cause cancer has led to two anti-cancer vaccines targeting infection by high-risk strains of human papillomaviruses (HPV) and by hepatitis B virus (HBV), as described by Stanley [19], which have already begun to reduce the incidence of these cancers in humans [20,21].…”

Section: Introductionmentioning

confidence: 99%

Human oncogenic viruses: nature and discovery

Chang

Moore

Weiss

2017

Phil. Trans. R. Soc. B

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Seven kinds of virus collectively comprise an important cause of cancer, particularly in less developed countries and for people with damaged immune systems. Discovered over the past 54 years, most of these viruses are common infections of humankind for which malignancy is a rare consequence. Various cofactors affect the complex interaction between virus and host and the likelihood of cancer emerging. Although individual human tumour viruses exert their malignant effects in different ways, there are common features that illuminate mechanisms of oncogenesis more generally, whether or not there is a viral aetiology. This article is part of the themed issue ‘Human oncogenic viruses’.

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“…In addition to their clinical importance as pathogens, HAdV can also be utilized scientifically and clinically as gene expression vectors, oncolytic agents, and vaccine vectors . Furthermore, the study of HAdV as a prototype DNA virus has provided fundamental insights into important cellular processes, including DNA replication, the cellular DNA damage response (DDR), and RNA processing . HAdV therefore present excellent opportunities to investigate fundamental aspects of DNA virus and cellular biology.…”

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confidence: 99%