Global profiling of histone modifications in the polyomavirus BK virion minichromosome

Fang, Chiung‐Yao; Shen, Cheng‐Huang; Wang, Meilin; Chen, Pei-Lain; Chan, Michael W.Y.; Hsu, Pang-Hung; Chang, Deching

doi:10.1016/j.virol.2015.04.009

Cited by 10 publications

(11 citation statements)

References 75 publications

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“…How viruses resist cellular chromatinization and silencing is known for only a few viruses (9,12,13). These include herpes simplex viruses (HSVs) (14)(15)(16), polyomaviruses (17,18), adenoviruses (19), and cytomegaloviruses (20,21), all of which encode proteins that promote transcriptionally activating histone modifications on chromatinized viral genomes during lytic infection.…”

Section: Viral Dna Introduced Into Cell Nuclei Is Exposed To Cellularmentioning

confidence: 99%

Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection

Mäntylä

Salokas

Oittinen

et al. 2016

J Virol

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The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging and in situ proximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, the two viral promoters in particular were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitors efficiently interfered with the expression of viral proteins and infection progress. Altogether, our data suggest that the acetylation of histones on parvoviral DNA is essential for viral gene expression and the completion of the viral life cycle. IMPORTANCEViral DNA introduced into cell nuclei is exposed to cellular responses to foreign DNA, including chromatinization and epigenetic silencing, both of which determine the outcome of infection. How the incoming parvovirus resists cellular epigenetic downregulation of its genes is not understood. Here, the critical role of epigenetic modifications in the regulation of parvovirus infection was demonstrated. We showed for the first time that a successful parvovirus infection is characterized by the deposition of nucleosomes with active histone acetylation on the viral promoter areas. The results provide new insights into the regulation of parvoviral gene expression, which is an important aspect of the development of parvovirus-based virotherapy. N uclear chromatin is composed of DNA and histone proteins (1). The histone proteins assemble DNA into nucleosomes, the composition and spacing of which contribute to higher-order chromatin packing. The chromatin is organized into regions of less-condensed actively transcribed chromatin (euchromatin) and highly condensed transcriptionally repressed chromatin (heterochromatin). Epigenetic modifications of histone proteins have been shown to correlate with the spatial distribution of active and repressed chromatin (2, 3). The acetylation of lysine 9 or 27 of histone H3 (H3K9ac and H3K27ac, respectively) and trimethylation of lysine 4 (H3K4me3) correlate with transcriptional activity, while repressed chromatin is characterized by, e.g., trimethylation or dimethylation of the same H3 lysine residues (H3K9me3 and H3K27me3 as well as H3K9me2 and H3K27me2) (4-8).Foreign DNA introduced into mammalian cells can be recognized as a threat by the host cell. The cellular responses to the foreign DNA, such as viral DNA, include the chromatinization of the entering DNA, leading to its transcriptional silencing (9-11). How viruses resist cellular chromatinization and silencing is known for only a few viruses (9, 12, 13). These include h...

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Section: Viral Dna Introduced Into Cell Nuclei Is Exposed To Cellularmentioning

confidence: 99%

Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection

Mäntylä

Salokas

Oittinen

et al. 2016

J Virol

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“… 160 BK virus minichromosome was identified to be hyperacetylated on histones 3, 2B, 2A, and 4, in addition to posttranslational modifications of various histones, for instance, methylation, phosphorylation, ubiquitination, and formylation. 161 In line with this, the histone acetyltransferase GCN5 expression was demonstrated to be increased during BK virus infection, which promotes viral pathogenesis and replication in human proximal tubular epithelial cells. This effect was countered by the use of the histone acetyltransferase inhibitor CPTH2, which resulted in a significant decrease in the major capsid protein VP1 expression, a marker of BK virus infection.…”

Section: Cancer-inducing Virusesmentioning

confidence: 56%

Targeting histone epigenetics to control viral infections

Nehme

Pasquereau

Herbein

2020

Histone Modifications in Therapy

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“…The activity of chromatin is highly modified by extensive posttranslational modifications (PTMs) of histones, which could greatly determine the efficacy of the early stages of viral infection. Early studies on polyomaviruses showed that virion associated histones are highly acetylated (27); this has been confirmed, and many additional modifications identified, by Fang and colleagues who mapped extensive post-translational modifications in the histones of the polyomavirus BKPyV virion particles and minichromosome using triton-acetic acid-urea (TAU)-polyacrylamide gel electrophoresis sepa-ration followed by nanoflow LC-MS/MS analysis (29). Notably, the authors found that N-terminal acetylation of histone H2A occurred only on the viral genome packaged in virions, and not of those in infected cells (29).…”

mentioning

confidence: 87%

The Promise of Proteomics in the Study of Oncogenic Viruses

McBride

2017

Molecular & Cellular Proteomics

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Oncogenic viruses are responsible for about 15% human cancers. This article explores the promise and challenges of viral proteomics in the study of the oncogenic human DNA viruses, HPV, McPyV, EBV and KSHV. These viruses have coevolved with their hosts and cause persistent infections. Each virus encodes oncoproteins that manipulate key cellular pathways to promote viral replication and evade the host immune response. Viral proteomics can identify cellular pathways perturbed by viral infection, identify cellular proteins that are crucial for viral persistence and oncogenesis, and identify important diagnostic and therapeutic targets.

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Global profiling of histone modifications in the polyomavirus BK virion minichromosome

Cited by 10 publications

References 75 publications

Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection

Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection

Targeting histone epigenetics to control viral infections

The Promise of Proteomics in the Study of Oncogenic Viruses

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