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marcstck wrote:Just to clear up one point about EBV that often leads to confusion, most people who are infected with the virus never had Mono. Often the infection can show up as a bad cold, or be completely asymptomatic.

To me, the most intriguing theory regarding why the herpes viruses are connected with MS and some other "autoimmune" diseases is that the presence of such "smoldering" infections reactivates normally dormant pieces of ancient retroviral DNA that are resident in the human genome.

Retroviruses do their dirty work by inserting their genes into the DNA of the cells they infect, and our evolutionary response to this has been to incorporate them into the human genome, as inactivated genes.

Anyway, there is growing evidence that in some humans with genetic predisposition, an infection of viruses in the herpes family actually activates some of this ancient viral genes in our own DNA, causing our own cells to express proteins that basically make the immune system go cannibal.

Here's an absolutely fascinating article on this phenomenon, entitled "The Insanity Virus". The title refers to schizophrenia, which also seems to be subject to this phenomenon, but there is much discussion of MS in the article as well…

http://discovermagazine.com/2010/jun/03 ... nity-virus

This is really a must-read…

Hi Marc,

Thanks for the article – fascinating indeed! And, as you say, it should be a "must-read." I've always had a special interest in the genetics of MS, due to my own family's being hit with 2 demyelinating diseases: MS (which I share with a cousin), and HNPP, a hereditary peripheral neuropathy I share with my dad and at least one other cousin (and maybe the cousin with MS as well).

I found the article's "Insanity Virus" (and possible MS trigger) even more interesting since I just found out that a couple of weeks ago yet another of my extended family members was dx'd with schizophrenia at the age of 20. That makes 3 relatives, from 3 different generations. Maybe my family's genes have been a particularly receptive DNA garbage dump (stew?).

The retrovirus referred to is specifically HERV-W, whose activation was linked separately to schizophrenia and to MS by two groups of researchers, and now the similarities are tied together a bit in the article – not tied neatly enough for a solution, but encouraging research, nonetheless. I’m glad that researchers are still looking hither, thither and yon whilst searching for answers.

Also of interest is that they suspect that HERV-W may be triggered initially shortly after birth in people with genetic predisposition to it – explaining why many of us (like me) don't recall having EBV or the other suspected triggers at all. The article's references to chronic infections that wax and wane beginning in childhood, are much more familiar to me than a single bout of disease that might have triggered MS soon afterwards.

My limited comprehension doesn't allow me to give a complete summary (even though I read it 3 times), but I've got to plug in a few short quotes to encourage more to read it – and add further input. I know HERV-W and retroviruses have been discussed at TIMS before.

It's not only that, as you say Marc, there's "much discussion of MS" in it, but that the researchers in the article often refer to both schizophrenia and MS together.

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Here are some random quotes from the Discover article that quickly caught my attention:

After eight years of research, Perron finally completed his retrovirus’s gene sequence. What he found on that day in 1997 no one could have predicted; it instantly explained why so many others had failed before him. We imagine viruses as mariners, sailing from person to person across oceans of saliva, snot, or semen—but Perron’s bug was a homebody. It lives permanently in the human body at the very deepest level: inside our DNA. After years slaving away in a biohazard lab, Perron realized that everyone already carried the virus that causes multiple sclerosis.
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Several other studies have since found similar active elements of HERV-W in the blood or brain fluids of people with schizophrenia. One, published by Perron in 2008, found HERV-W in the blood of 49 percent of people with schizophrenia, compared with just 4 percent of healthy people. “The more HERV-W they had,” Perron says, “the more inflammation they had.” He now sees HERV-W as key to understanding many cases of both MS and schizophrenia.
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Through this research, a rough account is emerging of how HERV-W could trigger diseases like schizophrenia, bipolar disorder, and MS. Although the body works hard to keep its ERVs under tight control, infections around the time of birth destabilize this tense standoff. Scribbled onto the marker board in Yolken’s office is a list of infections that are now known to awaken HERV-W—including herpes, toxoplasma, cytomegalovirus, and a dozen others. The HERV-W viruses that pour into the newborn’s blood and brain fluid during these infections contain proteins that may enrage the infant immune system. White blood cells vomit forth inflammatory molecules called cytokines, attracting more immune cells like riot police to a prison break. The scene turns toxic.

Whether people develop MS or schizophrenia may depend on how their immune system responds to HERV-W, he says. In MS the immune system directly attacks and kills brain cells, causing paralysis. In schizophrenia it may be that inflammation damages neurons indirectly by overstimulating them.

The first, pivotal infection by toxoplasmosis or influenza (and subsequent flaring up of HERV-W) might happen shortly before or after birth. That would explain the birth-month effect: Flu infections happen more often in winter. The initial infection could then set off a lifelong pattern in which later infections reawaken HERV-W, causing more inflammation and eventually symptoms. This process explains why schizophrenics gradually lose brain tissue. It explains why the disease waxes and wanes like a chronic infection. And it could explain why some schizophrenics suffer their first psychosis after a mysterious, monolike illness.

Thanks again, Marc. And eternal thanks for your blog - a refreshing, informative, and much appreciated voice of reason, intelligence, and most of all, humor.

P.S. My only personal brush with EBV was while sharing a college dorm room with my sister when she came down with a severe case of Mono and went home to sleep it off for a semester. Even though I had my usual monthly cold/swollen neck glands at the same time (just like I did as a child), I tested negative for EBV about 3 times.

I finally got my tonsils out at age 21, and at age 22 I was carried to the ER unable to walk from nerve spasms. I date my MS back at least to that episode.