Temporal Association of the Herpes Simplex Virus Genome with Histone Proteins during a Lytic Infection

Oh, Jae-Wook; Fraser, Nigel W.

doi:10.1128/jvi.00586-07

Cited by 123 publications

(161 citation statements)

References 30 publications

(42 reference statements)

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“…First, the entire naked DNA genome is exposed immediately after the invasion (35)(36)(37). Second, although the viral genome packages into chromatin with the host histones, it is less dense and much more loosely packed than the nuclear self-DNA (35)(36)(37). Importantly, we find that the relative binding affinity of IFI16 to various dsDNA fragments changes cooperatively not only with increasing IFI16 concentrations ( Fig.…”

Section: Discussionmentioning

confidence: 55%

“…Although the total amount of viral DNA would never exceed that of self-DNA, there are two features of foreign DNA that are much more conducive to filament formation by IFI16. First, the entire naked DNA genome is exposed immediately after the invasion (35)(36)(37). Second, although the viral genome packages into chromatin with the host histones, it is less dense and much more loosely packed than the nuclear self-DNA (35)(36)(37).…”

Section: Discussionmentioning

confidence: 99%

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Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy

Morrone

Wang²,

Constantoulakis³

et al. 2013

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

152

209

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Whether host DNA receptors have any capacity to distinguish self from nonself at the molecular level is an outstanding question in the innate immunity of mammals. Here, by using quantitative assays and electron microscopy, we show that cooperatively assembling into filaments on dsDNA may serve as an integral mechanism by which human IFN-inducible protein-16 (IFI16) engages foreign DNA. IFI16 is essential for defense against a number of different pathogens, and its aberrant activity is also implicated in several autoimmune disorders, such as Sjögren syndrome. IFI16 cooperatively binds dsDNA in a length-dependent manner and clusters into distinct protein filaments even in the presence of excess dsDNA. Consequently, the assembled IFI16·dsDNA oligomers are clearly different from the conventional noninteracting entities resembling beads on a string. The isolated DNA-binding domains of IFI16 engage dsDNA without forming filaments and with weak affinity, and it is the non-DNA-binding pyrin domain of IFI16 that drives the cooperative filament assembly. The surface residues on the pyrin domain that mediate the cooperative DNA binding are conserved, suggesting that related receptors use a common mechanism. These results suggest that IFI16 clusters into signaling foci in a switch-like manner and that it is capable of using the size of naked dsDNA as a molecular ruler to distinguish self from nonself.cooperative filament formation | inflammasome R ecognition of foreign intracellular DNA is a widely conserved defense mechanism by which the innate immune system of mammals detects and responds to invading pathogens (1, 2). Using such a universal molecule as a major danger signal for detecting pathogens must be regulated in a stringent yet efficient manner. However, only a few deciding factors are known for the host innate immune system to selectively engage foreign DNA (i.e., nonself-DNA) while minimizing interactions with self-DNA, which include the compartmentalization of mammalian cells and the size of foreign DNA. These features, however, only raise more questions than provide answers. For example, the footprints of intracellular DNA receptors usually fall below 20 bp, and yet a long foreign DNA fragment [e.g., poly(dA:dT); ≥1,000 bp] is required to induce a robust innate immune response even in a normally DNA-free environment like the cytoplasm (1, 2). On the other hand, foreign DNA-sensing pathways also exist in the host nucleus in which DNA receptors must not respond to abundant self-DNA to prevent spurious activities (1, 2). Indeed, one of the major unresolved questions in understanding the DNA-sensing pathways of mammals is whether the host intracellular DNA receptors have any capacity to distinguish self-from nonself-DNA at the molecular level (2).Human IFN inducible protein-16 (IFI16) is an intracellular DNA receptor of innate immunity that belongs to the family of absent-in-melanoma-2 (AIM2)-like receptors (ALRs) (1-4). IFI16 senses DNA from invading pathogens in both the nucleus and cytoplasm [e.g., vaccinia virus...

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy

Morrone

Wang²,

Constantoulakis³

et al. 2013

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

152

209

View full text Add to dashboard Cite

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“…Although the levels of nucleosomes on the genome appear to be reduced relative to cellular DNA at later times in infection (36,40), the absolute amount of viral DNA associated with histones increases during replication (36). Additionally, it has also been observed that histone H3.1 is incorporated in a replication dependent manner (39), indicating that some level of histone assembly occurs on replicated viral DNA.…”

mentioning

confidence: 96%

Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components

Peng

Nogueira

Vogel

et al. 2010

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

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The cellular transcriptional coactivator HCF-1 interacts with numerous transcription factors as well as other coactivators and is a component of multiple chromatin modulation complexes. The protein is essential for the expression of the immediate early genes of both herpes simplex virus (HSV) and varicella zoster virus and functions, in part, by coupling chromatin modification components including the Set1 or MLL1 histone methyltransferases and the histone demethylase LSD1 to promote the installation of positive chromatin marks and the activation of viral immediately early gene transcription. Although studies have investigated the role of HCF-1 in both cellular and viral transcription, little is known about other processes that the protein may be involved in. Here we demonstrate that HCF-1 localizes to sites of HSV replication late in infection. HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b, a protein that regulates the progression of cellular DNA replication forks via chromatin reorganization. Asf1b localizes with HCF-1 in viral replication foci and depletion of Asf1b results in significantly reduced viral DNA accumulation. The results support a model in which the transcriptional coactivator HCF-1 is a component of the HSV DNA replication assembly and promotes viral DNA replication by coupling Asf1b to DNA replication components. This coupling provides a novel function for HCF-1 and insights into the mechanisms of modulating chromatin during DNA replication.

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“…Upon HSV-1 infection, viral genomes enter the nucleus and become "chromatinized" as the non-nucleosomal state is transformed into a chromatin structure that resembles the host genome (3,5). The assembly and modulation of nucleosomes during infection is dependent on a plethora of viral and host chromatin components (6).…”

Section: Herpes Simplex Virus (Hsv-1)mentioning

confidence: 99%

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection

Kulej

Avgousti

Sidoli

et al. 2017

Molecular & Cellular Proteomics

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Herpes simplex virus (HSV-1) lytic infection results in global changes to the host cell proteome and the proteins associated with host chromatin. We present a system level characterization of proteome dynamics during infection by performing a multi-dimensional analysis during HSV-1 lytic infection of human foreskin fibroblast (HFF) cells. Our study includes identification and quantification of the host and viral proteomes, phosphoproteomes, chromatin bound proteomes and post-translational modifications (PTMs) on cellular histones during infection. We analyzed proteomes across six time points of virus infection (0, 3, 6, 9, 12 and 15 h post-infection) and clustered trends in abundance using fuzzy c-means. Globally, we accurately quantified more than 4000 proteins, 200 differently modified histone peptides and 9000 phosphorylation sites on cellular proteins. In addition, we identified 67 viral proteins and quantified 571 phosphorylation events (465 with high confidence site localization) on viral proteins, which is currently the most comprehensive map of HSV-1 phosphoproteome. We investigated chromatin bound proteins by proteomic analysis of the high-salt chromatin fraction and identified 510 proteins that were significantly different in abundance during infection. We found 53 histone marks significantly regulated during virus infection, including a steady increase of histone H3 acetylation (H3K9ac and H3K14ac). Our data provide a resource of unprecedented depth for human and viral proteome dynamics during infection. Collectively, our results indicate that the proteome composition of the chromatin of HFF cells is highly affected during HSV-1 infection, and that phosphorylation events are abundant on viral proteins. We propose that our epi-proteomics approach will prove to be important in the characterization of other model infectious systems that involve changes to chromatin composition. Molecular & Cellular Proteomics 16: 10.1074/mcp.M116.065987, S92-S107, 2017. Herpes simplex virus (HSV-1)1 leads to a contagious and persistent infection that affects about 95% of the human population. The HSV-1 genome is a double-stranded DNA molecule that replicates in the host cell nucleus (1). HSV-1 initially infects epithelial cells as a lytic infection, and then enters peripheral neurons where it establishes latency (2, 3). Processes such as viral transcription, viral DNA synthesis, virion assembly and DNA packaging take place in discrete virus-induced structures within the nucleus called replication compartments (1, 4). These processes are temporally regulated by the viral cascades of immediate-early (IE), early (E), and late (L) gene expression. The IE proteins are primarily responsible for counteracting intrinsic host defenses and for activating expression of early-phase genes (1). Early viral pro-

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Temporal Association of the Herpes Simplex Virus Genome with Histone Proteins during a Lytic Infection

Cited by 123 publications

References 30 publications

Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy

Cooperative assembly of IFI16 filaments on dsDNA provides insights into host defense strategy

Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components

Time-resolved Global and Chromatin Proteomics during Herpes Simplex Virus Type 1 (HSV-1) Infection

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