1. Patients launch $1.27 million crowdfunding campaign for ME/CFS gut microbiome study.
    Check out the website, Facebook and Twitter. Join in donate and spread the word!
9th Invest in ME International ME Conference, 2014 - Part 2: Pathogens and the Gut
Mark Berry continues his series of articles on the 9th Invest in ME International ME Conference in London, with the emphasis shifting from autoimmunity to pathogens and the gut ...
Discuss the article on the Forums.

Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortal

Discussion in 'Other Health News and Research' started by Ecoclimber, Jul 27, 2014.

  1. Ecoclimber

    Ecoclimber Senior Member

    Messages:
    609
    Likes:
    980
    Mercer Island Wa
    J Virol. 2014 Jul 23. pii: JVI.00972-14. [Epub ahead of print]
    Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
    Birdwell CE1, Queen KJ1, Kilgore P2, Rollyson P3, Trutschl M2, Cvek U2, Scott RS4.

    Abstract
    The oral cavity is a persistent reservoir for Epstein-Barr virus (EBV) with lifelong infection of resident epithelial and B cells.
    Infection of these cell types results in distinct EBV gene expression patterns regulated by epigenetic modifications involving DNA methylation and chromatin structure.

    Regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may result in long-lasting host epigenetic reprogramming.

    To identify epigenetic events following EBV infection, a transient infection model was established to map epigenetic changes in telomerase-immortalized oral keratinocytes.

    EBV-infected oral keratinocytes exhibited a predominantly latent viral gene expression program with some lytic or abortive replication. Calcium and methylcellulose-induced differentiation was delayed in EBV-positive and in clones that lost EBV compared to uninfected controls, indicating a functional consequence of EBV epigenetic modifications.

    Analysis of global cellular DNA methylation identified over 13,000 differentially methylated CpG residues in cells exposed to EBV compared to uninfected controls, with CpG island hypermethylation observed at several cellular genes.

    Although the vast majority of the DNA methylation changes were silent, 65 cellular genes that acquired CpG methylation showed altered transcript levels. Genes with increased transcript levels frequently acquired DNA methylation within the gene body while those with decreased transcript levels acquired DNA methylation near the transcription start site.

    Treatment with the DNA methyltransferase inhibitor, decitabine, restored expression of some hypermethylated genes in EBV-infected and EBV-negative transiently-infected clones.

    Overall, these observations suggested that EBV infection of keratinocytes leaves a lasting epigenetic imprint that can enhance the tumorigenic phenotype of infected cells.

    IMPORTANCE:
    Here we show that EBV infection of oral keratinocytes led to CpG island hypermethylation as an epigenetic scar of prior EBV infection that was retained after loss of the virus.

    Such EBV-induced epigenetic modification recapitulated the hypermethylated CpG island methylator phenotype (CIMP) observed in EBV-associated carcinomas.

    These epigenetic alterations not only impacted gene expression but resulted in delayed calcium and methylcellulose-induced keratinocyte differentiation.

    Importantly, these epigenetic changes occurred in cells that were not as genetically unstable as carcinoma cells indicating that EBV infection induced an epigenetic mutator phenotype.

    The impact of this work is that we have provided a mechanistic framework for how a tumor virus using the epigenetic machinery can act in a "hit-and-run fashion" with retention of epigenetic alterations after loss of the virus.

    Unlike genetic alterations, these virally-induced epigenetic changes can be reversed pharmacologically providing therapeutic interventions to EBV-associated malignancies.

    Ties to another research article on how lytic EBV infection can subvert the human immune system by by expressing BPLF1 enzyme to counteract TLR's 2,3,7,9
    http://forums.phoenixrising.me/inde...nic-fatigue-syndrome.27634/page-3#post-438264
    Last edited: Jul 28, 2014
  2. alex3619

    alex3619 Senior Member

    Messages:
    7,017
    Likes:
    10,779
    Logan, Queensland, Australia
    Its also important because such changes might cause diseases like ME.
    NK17, snowathlete and Valentijn like this.
  3. stevesayshi

    stevesayshi

    Messages:
    97
    Likes:
    72
    Yeah, I wonder what it can do to the brain. I was never quite "the same" after I got EBV when I was 18 - 19. More apathetic, lethargic, slightly dumber, etc. The messed up thing is that I just accepted that was how it was gonna be.
    Sushi and NK17 like this.
  4. alex3619

    alex3619 Senior Member

    Messages:
    7,017
    Likes:
    10,779
    Logan, Queensland, Australia
    If EBV can reprogram B cells, can it reprogram microglia?"
    Sushi, SOC and NK17 like this.
  5. anciendaze

    anciendaze Senior Member

    Messages:
    859
    Likes:
    879
    Note that the abstract refers to both lytic and abortive infection. There appears to be an assumption that immortalized cells have rid themselves of virus. (Am I reading this wrong?) We are still in the dark concerning actual viral persistence in immune cells, despite some evidence that EBV can subvert antibody response on which common tests for active EBV infection are based. Considering the prevalence of EBV in humans, and life-long persistence by related HSV, CMV, VZV and HHV6, this is a major gap in research. HHV6 can even be found integrated into chromosomes of about 1% of humans, though usually in telomeres.

    If we know so little about the most common human viruses, what does that tell you about the state of the art?
    ukxmrv, Sushi, SOC and 2 others like this.
  6. alex3619

    alex3619 Senior Member

    Messages:
    7,017
    Likes:
    10,779
    Logan, Queensland, Australia
    Swiss cheese?
    Sushi likes this.

See more popular forum discussions.

Share This Page