Innate Sensing of DNA Virus Genomes

Ma, Zhe; Ni, Guo‐Xin; Damania, Blossom

doi:10.1146/annurev-virology-092917-043244

Cited by 106 publications

(101 citation statements)

References 157 publications

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“…Structurally, IFI16 has two HIN200 domains, HINa and HINb, which are connected via a linker region. In addition to double‐stranded DNA, IFI16 also binds single‐stranded DNA via the HINa domain, and preferentially binds quadraplex DNA structures that are intrinsic to many viral genomes and GC‐rich DNA . Although IFI16 is predominately located in the nucleus, it can shuttle between the nucleus and the cytoplasm, where it has other functions .…”

Section: Alrmentioning

confidence: 99%

“…In addition to double-stranded DNA, IFI16 also binds singlestranded DNA via the HINa domain, and preferentially binds quadraplex DNA structures that are intrinsic to many viral genomes and GC-rich DNA. 34 Although IFI16 is predominately located in the nucleus, it can shuttle between the nucleus and the cytoplasm, where it has other functions. 32 Although IFI16 has additional DNA sensing roles in the cytoplasm, there is no evidence that it forms an inflammasome from detection of cytosolic DNA.…”

Section: Ifi16 Inflammasomementioning

confidence: 99%

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Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Marchesan

Girnary

Moss

et al. 2019

Periodontology 2000

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Inflammasomes are a group of multimolecular intracellular complexes assembled around several innate immune proteins. Recognition of a diverse range of microbial, stress and damage signals by inflammasomes results in direct activation of caspase‐1, which subsequently induces the only known form of secretion of active interleukin‐1β and interleukin‐18. Although the importance of interleukin‐1β in the periodontium is not questioned, the impact of inflammasomes in periodontal disease and its potential for therapeutics in periodontology is still in its very early stages. Increasing evidence in preclinical models and human data strongly implicate the involvement of inflammasomes in a number of inflammatory, autoinflammatory and autoimmune disorders. Here we review: (a) the currently known inflammasome functions, (b) clinical/preclinical data supporting inflammasome involvement in the context of periodontal and comorbid diseases and (c) potential therapies targeting inflammasomes. To clarify further the inflammasome involvement in periodontitis, we present analyses of data from a large clinical study (n = 5809) that measured the gingival crevicular fluid‐interleukin‐1β and grouped the participants based on current periodontal disease classifications. We review data on 4910 European‐Americans that correlate 16 polymorphisms in the interleukin‐1B region with high gingival crevicular fluid‐interleukin‐1β levels. We show that inflammasome components are increased in diseased periodontal tissues and that the caspase‐1 inhibitor, VX‐765, inhibits ~50% of alveolar bone loss in experimental periodontitis. The literature review further supports that although patients clinically present with the same phenotype, the disease that develops probably has different underlying biological pathways. The current data indicate that inflammasomes have a role in periodontal disease pathogenesis. Understanding the contribution of different inflammasomes to disease development and distinct patient susceptibility will probably translate into improved, personalized therapies.

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Section: Alrmentioning

confidence: 99%

Section: Ifi16 Inflammasomementioning

confidence: 99%

Role of inflammasomes in the pathogenesis of periodontal disease and therapeutics

Marchesan

Girnary

Moss

et al. 2019

Periodontology 2000

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“…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].…”

mentioning

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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“…Following successful viral entry and import of the viral genome into the nucleus, several challenges must be overcome to begin replicating. Viral genomes must avoid cellular intrinsic antiviral defenses and homeostatic regulatory pathways such as the DDR that respond to the presence of foreign DNA and act to suppress viral gene expression and DNA replication (See also the review by Sohn & Hearing in this issue). Incoming HAdV genomes that avoid restriction by cellular pathways undergo replication and initiate VRC formation in close proximity to nuclear bodies (NBs) marked by the promyelocytic leukemia (PML) protein .…”

Section: The Fate Of Incoming Viral Genomesmentioning

confidence: 99%