The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition.

Ishov, Alexander M.; Maul, Gerd G.

doi:10.1083/jcb.134.4.815

Cited by 314 publications

(364 citation statements)

References 63 publications

(94 reference statements)

Supporting

Mentioning

346

Contrasting

Unclassified

Order By: Relevance

“…Concomitantly, both the number and size of the ND10 bodies increase (13,14). ii) As noted above, newly synthesized ICP0 colocalizes with ND10 bodies.…”

Section: Dna Binding Proteins | Gene Derepressionmentioning

confidence: 87%

See 1 more Smart Citation

Use of biotinylated plasmid DNA as a surrogate for HSV DNA to identify proteins that repress or activate viral gene expression

Mallon¹,

Wakim²,

Roizman³

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

ICP0, a key herpes simplex virus regulatory protein, functions first in the nucleus and then in the cytoplasm. The duration of its nuclear sojourn in cells transfected with DNA and then infected is related to the quantity of transfected DNA. Furthermore, ICP0 transactivates both viral genes and genes encoded by the transfected DNA. The data support the hypothesis that ICP0 is retained in the nucleus until it completes the replacement of repressive chromatin with effector proteins that enable transcription of both DNA templates. To identify the effector proteins, we transfected cells with biotinylated DNA encoding a nonviral gene and then infected the cells with wild-type virus. Proteins bound to transfected biotinylated plasmid recovered from mock-treated and infected cells were identified using mass spectrometry followed by appropriate database search. The transfected DNA from mock-infected cells yielded proteins associated with repression, whereas DNA recovered from infected cells included proteins known to enable transcription and proteins that have not been previously associated with that role. To test the hypothesis that the proteins hitherto not known to associate with viral gene expression are nevertheless essential, we tested the role of the DEAD-box helicase Ddx17. We report that Ddx17 plays a critical role in the expression of early and late viral genes. Thus, biotinylated DNA recovered from transfected infected cells can function as a surrogate for viral DNA and is a rich source of proteins that play a role in viral gene expression but which have not been previously identified in that role. DNA binding proteins | gene derepressionU pon entry into the nucleus, the DNA of HSV-1 is immediately coated by repressive cellular proteins and bound to a dynamic nuclear body known as ND10 (1). Expression of viral genes requires sequential derepression at least at two checkpoints (2). In the first VP16, a viral tegument protein introduced into the cell during infection, recruits to the promoters of the α (immediate early) genes numerous host proteins that include the Octamer binding protein 1, Host cell factor 1, and Lysine Specific Demethylase 1 (LSD1) (1, 2). The consequence of derepression of the α genes is the synthesis of the six α proteins. One of these proteins, ICP0, plays a key role in the transition through the second checkpoint. Briefly, newly synthesized ICP0 colocalizes with ND10, recruits the ubiquitin-conjugating enzyme UbcH5a, and mediates the degradation of PML and SP100, key components of the ND10 nuclear bodies (3-5). In addition, it interacts with a repressor complex whose key components are HDAC-1/2, CoREST, LSD1, and REST. In this instance ICP0 binds to CoREST and dislodges HDAC-1/2 from the repressor complex (6-8). Last, ICP0 either recruits or enhances the recruitment of numerous host proteins to the viral replication compartment erected in the space formerly occupied by the ND10 nuclear bodies. These include cyclin D3, cdc34, CoREST, USP7, Bmal1, and the histone acetyl transferase CLOCK (...

show abstract

“…Concomitantly, both the number and size of the ND10 bodies increase (13,14). ii) As noted above, newly synthesized ICP0 colocalizes with ND10 bodies.…”

Section: Dna Binding Proteins | Gene Derepressionmentioning

confidence: 87%

“…First, it binds the UbcH5A ubiquitin-conjugating protein to degrade the ND10 proteins PML and SP100, leading to inactivation of ND10 functions (3,4). Second, it derepresses the DNAs aggregated at the ND10 bodies to enable the expression of β and γ genes (13,14). This report is based on the results of studies on the functions of ICP0.…”

Section: Discussionmentioning

confidence: 99%

Use of biotinylated plasmid DNA as a surrogate for HSV DNA to identify proteins that repress or activate viral gene expression

Mallon¹,

Wakim²,

Roizman³

2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…ATRX is a component of the PML nuclear body (PML-NB), which is the nuclear localization site of many DNA viruses, including herpes simplex virus 1 (HSV-1), human cytomegalovirus and adenovirus 5 [65]. ATRX is also associated with herpesvirus infections.…”

Section: Discussionmentioning

confidence: 99%

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Zeng

Huang

et al. 2014

Sci. China Life Sci.

View full text Add to dashboard Cite

Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC) tumorigenesis. However, the mechanism(s) connecting EBV infection and NPC remain unclear. Recently, a new class of EBV microRNAs (miRNAs) has been described. To determine how EBV miRNAs control the expression of host genes, and to understand their potential role in NPC tumorigenesis, we profiled the expression of 44 mature EBV miRNAs and potential host genes in NPC and non-tumor nasopharyngeal epithelial tissues. We found that 40 EBV miRNAs from the BART transcript were highly expressed in NPC. Analysis of potential BART miRNA target genes revealed that 3140 genes and several important pathways might be involved in the carcinogenesis of NPC. A total of 105 genes with potential EBV miRNA binding sites were significantly downregulated, suggesting that EBV miRNAs may regulate these genes and contribute to NPC carcinogenesis. An EBV miRNA and host gene regulation network was generated to provide useful clues for validating of EBV miRNA functions in NPC tumorigenesis.

show abstract

“…Previous studies identified the PML protein as the defining factor of ND10 structures since it functions as a kind of scaffold protein that is responsible for the assembly and maintenance of this domain and recruits other ND10-associated proteins like hDaxx to this subnuclear structure (25,53). For a long time, this subcellular compartment, which colocalizes with sites where the input viral genome of various DNA viruses (herpesviruses, adenoviruses, and papovaviruses) accumulates, was hypothesized to be essential for HCMV replication since only viral DNA deposited at ND10 had been demonstrated to initiate transcription (24,37). In contrast, several lines of evidence likewise implicated these nuclear substructures to be involved in host antiviral defenses.…”

mentioning

confidence: 99%

Nuclear Domain 10 Components Promyelocytic Leukemia Protein and hDaxx Independently Contribute to an Intrinsic Antiviral Defense against Human Cytomegalovirus Infection

Tavalai

Papior

Rechter

et al. 2008

J Virol

114

142

View full text Add to dashboard Cite

Infection with DNA viruses commonly results in the association of viral genomes with a cellular subnuclear structure known as nuclear domain 10 (ND10). Recent studies demonstrated that individual ND10 components, like hDaxx or promyelocytic leukemia protein (PML), mediate an intrinsic immune response against human cytomegalovirus (HCMV) infection, strengthening the assumption that ND10 components are part of a cellular antiviral defense mechanism. In order to further define the role of hDaxx and PML for HCMV replication, we generated either primary human fibroblasts with a stable, individual knockdown of PML or hDaxx (PML-kd and hDaxx-kd, respectively) or cells exhibiting a double knockdown. Comparative analysis of HCMV replication in PML-kd or hDaxx-kd cells revealed that immediate-early (IE) gene expression increased to a similar extent, regardless of which ND10 constituent was depleted. Since a loss of PML, the defining component of ND10, results in a dispersal of the entire nuclear substructure, the increased replication efficacy of HCMV in PML-kd cells could be a consequence of the dissociation of the repressor protein hDaxx from its optimal subnuclear localization. However, experiments using three different recombinant HCMVs revealed a differential growth complementation in PML-kd versus hDaxx-kd cells, strongly arguing for an independent involvement in suppressing HCMV replication. Furthermore, infection experiments using double-knockdown cells devoid of both PML and hDaxx illustrated an additional enhancement in the replication efficacy of HCMV compared to the single-knockdown cells. Taken together, our data indicate that both proteins, PML and hDaxx, mediate an intrinsic immune response against HCMV infection by contributing independently to the silencing of HCMV IE gene expression.

show abstract

The periphery of nuclear domain 10 (ND10) as site of DNA virus deposition.

Cited by 314 publications

References 63 publications

Use of biotinylated plasmid DNA as a surrogate for HSV DNA to identify proteins that repress or activate viral gene expression

Use of biotinylated plasmid DNA as a surrogate for HSV DNA to identify proteins that repress or activate viral gene expression

Regulation network and expression profiles of Epstein-Barr virus-encoded microRNAs and their potential target host genes in nasopharyngeal carcinomas

Nuclear Domain 10 Components Promyelocytic Leukemia Protein and hDaxx Independently Contribute to an Intrinsic Antiviral Defense against Human Cytomegalovirus Infection

Contact Info

Product

Resources

About