Viral Etiquette Tips : The Epigenetic Effects of Life Long Guests

Hello E3 scientists! Here are three etiquette tips for the modern virus. This week’s post is a bit of “tongue in cheek”, while pointing out some neat virology & epigenetics research!!!

Viral Etiquette tip #1 Practice self control, don’t interrupt your host’s epigenome event plans.

Epstein-Barr virus (EBV) has guest behavior which exemplifies this tip – relatively non-symptomatic replication phases in most hosts, and long lifetime latency phases. Most humans barely know they have it, yet 90% of them do. Still, EBV can slip up. Recent studies are spotlighting EBV’s epigenetic tightrope walk.

EBV practices self control by the interaction of its transcription factor protein Zta by “two routes”. The Zta protein is expressed only during infection and just before lytic replication – co-ordinating with the methylation state of the EBV genome to control replication. Zta binds with methylated CpG-containing DNA response elements, called Zta response elements (or ZREs) at the promoters of EBV viral lytic cycle genes (1). Zta also binds within H3K9m3-associated chromatin in vivo (2). These dual actions enact appropriate, viral replication.

Unfortunately EBV does rarely slip up, causing slight associations with Burkitts lymphoma and Hodgkins. Latent EBV can initiate suppression of host tumor suppressor Bim, first by histone modification then promoter methylation – as found in Burkitt’s lymphoma biopsies (3). This is an example oncogenic viral action on our epigenome. This type of guest should get the boot!

Viral Etiquette tip #2 Silence is golden.

While altering your host cell’s epigenome to promote survival may seem courteous, it’s just the opposite. It’s really best to be more of a quiet listener, shall we say, in any cellular conversation. Haven’t we all gotten stuck at some point, listening to a monologuing bore? However, even a “me monster” virus, can offer an unintended advantage to its host for cancer treatment. Enter the boot. This fascinating article in Science Daily, Sept. 27^th 2011 describes the work of Ninib Baryawno et al, at the Karolinska Institutet in Sweden, (4) which shows that CMV is present in medullablastomas, and antiviral/combinational treatments reduce tumor growth by 40% to 70%!

Viral Etiquette tip #3 Bring a hostess gift.

A healthly immune response is the best gift to a host! Sounds far fetched for a virus? Maybe not! There is evidence that periodic viral replication cycles, can keep host immune systems fit to fight. See Herpesvirus latency confers symbiotic protection from bacterial infection. Erik S. Barton et al. (17 May 2007) Nature. Mice infected with mouse viruses, versions which were similar to Epstein-Barr and Cytomegalovirus, gained immune resistance to Plague and Listeria, via sustained up regulation of antiviral cytokine interferon, and systemic activation of macrophages (5).

All you scientist human hosts, please do consider signing into our “guest book”, by signing up as a new member of the E3 scientific network!

Best regards,

-Nicole

1. Epigenetic Control of Viral Life-Cycle by a DNA-Methylation Dependent Transcription Factor.(October 2011) PloS one Kirsty Flower et al.
2. Dynamic Chromtin Environment of Key Lytic Cycle Regulatory Regions of the Epstein-Barr Virus Genome. (Nov. 2011) J. Virology Ramasubramanyan, S. et al.
3. Epstein-Barr Virus Latency in B Cells Leads to Epigenetic Repression and CpGMethylation of the Tumour Suppressor Gene Bim. (2009) PLoS Pathogens. Paschos, K et al.
4. Detection of human cytomegalovirus in medulloblastomas reveals a potential therapeutic target. (2011) Journal of Clinical Investigation, Ninib Baryawno et al.
   
5. Herpesvirus latency and Symbiotic Protection from Bacterial Infection. (2009) Viral Immunology, Erik S. Barton, Douglas W. White, and Herbert W. Virgin

Flower K, Thomas D, Heather J, Ramasubramanyan S, Jones S, & Sinclair AJ (2011). Epigenetic Control of Viral Life-Cycle by a DNA-Methylation Dependent Transcription Factor. PloS one, 6 (10) PMID: 22022468

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