Simmaron Research blog post, by Cort Johnson, 30 April 2018: The Autoimmune Virus? Groundbreaking EBV Finding Could Help Explain ME/CFS
Viral Mystery
“I’ve been a co-author in almost 500 papers. This one is more important than all of the rest put together. It is a capstone to a career in medical research,” Harley
I sensed some awe in Ron Davis’s voice as he pushed for more understanding of Epstein-Barr Virus’s effects in ME/CFS during a talk at the Brain Science conference. Davis is not to my knowledge finding much evidence of EBV reactivation in the severe ME/CFS patient study – a surprise – but he is very interested in what happened during that initial EBV infection, which appears to have triggered chronic fatigue syndrome (ME/CFS) in so many people.
He’s not alone in his “admiration” for the virus. Simmaron’s Advisor, Dr. Daniel Peterson, whose clinical practice and research stemmed from an outbreak in the Lake Tahoe region of Chronic Fatigue Syndrome, has tracked EBV in patients for decades, noting very high titers to EBV and other herpes viruses in subsets of patients.
It’s not surprising that these two important figures have had their eyes on EBV. EBV, after all, is kind of in a league of its own. An invader of B and epithelial cells, the 50th anniversary of its discovery was recently celebrated with numerous reviews. Epstein-Barr was discovered in 1966 by Anthony Epstein and Yvonne Barr. It was the first human virus shown to cause cancer. The sequencing of its large genome in 1995 helped launch the genomic era.
One of the more massive and complicated viruses, it’s one of the very few viruses that’s able to avoid elimination: once EBV infects your B-cells, it’s in your body to stay. It’s able to effectively hide from the immune system and reactivate just enough so that when the infected B-cells die it can move on to other cells.
We’re well equipped to ward off EBV when we’re young – it usually produces only minor symptoms – but as our immune systems alter as we age, that changes. Encountering EBV as an adolescent or adult (infectious mononucleosis, glandular fever) – as increasingly happens in our germ phobic age – often means months of convalescence as our immune systems struggle to ward off this powerful virus.
The problems don’t stop there. We know that infectious mononucleosis (IM) is a common trigger of ME/CFS but coming down with IM/glandular fever in adolescence has also been shown to increase one’s risk of coming down with multiple sclerosis 2-4 fold and lupus by fifty percent. Because of EBV’s ability to remain latent in the body, EBV reactivations are a huge problem for transplant patients with compromised immune systems.
The big question concerning EBV is how a virus which has essentially been latent for decades could contribute to serious diseases like MS and lupus. We now may have the answer. Last week, what will probably turn out to be a seminal paper in pathogen research directly showed for the first time how EBV appears to be able to trigger autoimmune diseases later in life and could conceivably play a role in ME/CFS.
The rather hum drum title of the paper “Transcription factors operate across disease loci with EBNA2 implicated in autoimmunity” in the Nature Genetics Journal hardly hinted at the possibilities the paper presents.
Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity John B. Harley, Xiaoting Chen, Mario Pujato, Daniel Miller, Avery Maddox, Carmy Forney, Albert F. Magnusen, Arthur Lynch, Kashish Chetal, Masashi Yukawa, Artem Barski, Nathan Salomonis, Kenneth M. Kaufman, Leah C. Kottyan & Matthew T. Weirauch. Nature Genetics (2018) doi:10.1038/s41588-018-0102-3
EBV consists of several proteins of which EBNA-2 is one. EBNA-2 is EBV’s main viral transactivator; i.e. it’s a transcription factor that turns on genes in an infected cell that help EBV to survive. Essentially EBNA-2 allows EBV to hijack a cell’s genetics and put them to its own use.
The study – produced by researchers at Cinncinnati’s Children Hospital – demonstrated that once EBV infects B-cells, it turns on genes that have been identified as risk factors for a boatload of autoimmune diseases.
It turns out that even though the virus is, so to speak, latent; i.e. it’s not replicating – its transcription factor is still active – altering the expression of our genes. The genes that it affects just happen to be the same genes that increase the risk of developing lupus, multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes. Apparently decades of genetic assault from EBV’s transcription factor can set the stage or at least contribute to many autoimmune diseases.
Chronic diseases are usually caused by a variety of genetic and environmental factors. Because not everyone with these transcription factors comes down with a chronic illness, other factors must play a role. The authors believe, though, that the gene expression changes induced by the virus in the B cells could account for a large number of people with lupus and MS who fall ill.
“In lupus and MS, for example, the virus could account for a large percentage of those cases. We do not have a sense of the proportion in which the virus could be important in the other EBNA2-associated diseases,” Harley
Read more about the ME/CFS and research into the EBV virus
