February 6, 2013 A More Science-y Look at What’s Causing MS
You know when I promise that I’ll post a certain thing on here and then blatantly disregard myself? I’m going to stop doing that. So, as promised a while ago, here’s a thing I wrote for a neuro class last semester that investigates the link between MS and mono! It’s terrifying! Actually! Don’t get mono! It’s accessible to non-science people and all the terminology is explained so don’t worry about that. I’m gonna stick a page break in so you’ll have to click through, so go for it. Enjoy. And by enjoy what I mean is become scared of mono. And frustrated by the CDC.
PAGE BREAK PAGE BREAK CLICK THROUGH TIME
Investigating the link between a common virus and Multiple Sclerosis, or the dangers of adolescent mononucleosis
It has become evident over the past several years that there is some link between the Epstein-Barr virus (EBV, the virus that causes mononucleosis) and multiple sclerosis (MS). One study in 2009 even found that 100% of the MS patients in the study had been infected with EBV at some point prior to their MS diagnosis#. But what, exactly, is the link between the two? With a virus as widespread as EBV and a condition as (comparatively) rare as multiple sclerosis, is attempting to find a link between the two realistic? In a recent paper, a lab in Italy details their findings related to the linkage.
Multiple sclerosis is a neurodegenerative autoimmune disease which can cause seemingly any disability. Approximately 400,000 Americans have MS#. The disease is characterized by a loss of myelin, the sheath which covers nerves, in both the central and peripheral nervous systems. While other factors, such as vitamin D deficiency#, are strongly linked to the onset of MS, the percentages suggesting EBV linkage are too high to ignore. EBV, according to the official CDC page, is an extremely contagious and common virus, with up to 95% of adults between the ages of 35 and 40 in the United States having been infected at some point. It should be noted that the page stresses the mild nature of the virus and does not, at any point, mention potential linkage to multiple sclerosis. The page also has not been updated since 2006#.
The key to understanding why the EBV linkage is relevant to MS despite the differences in incidence between the two conditions is the type of EBV. EBV does not necessarily always result in infectious mononucleosis (IM), but when it does, and when IM occurs in late adolescence or early adulthood, the risk of MS increases between two-to-fourfold.
The lab in Italy, in its efforts to research the linkage, identified two elements (based on prior research elsewhere) caused by the EBV that could be viral sources of MS. Both come from the W family of human endogenous retroviruses (HERV-W). One, known as the MSRV element (MS-associated retrovirus) (to be referred to as MSRVenv from now on), was found in the cells of MS patients and purified for use in studies. The MSRVenv element, once extracted and purified, exists as a free virus-like particles. The other element is an element located on a chromosome which does not form virus-like particles. The product of this element has been named syncytin-1. Syncytin-1 and MSRVenv, despite their differences in particle forms, share >94% of identities at the RNA level.
MSRVenv and syncytin-1 are both pro-inflammatory and capable of causing neuroinflammation, neurodegeneration, and alterations to both the immune system and stress responses. All of these suggest that either or both of these elements could trigger multiple sclerosis.
Corroborating this thought, MS patients whose spinal fluid tested positively for MSRV presence typically experience a worse prognosis, faster disease progression, higher mean disability status, higher annual relapse rate, and higher incidence of progression to progressive MS (from relapsing-remitting). Similarly, patients who first presented with optic neuritis (an inflammation of the optic nerve which can occur in patients with MS or can be a precursor to MS) who tested positively for MSRV presence converted to “full-blown MS” in the next 20 months after testing.
Prior studies, however, had failed to prove the association between EBV and MS sufficiently, and also had not determined whether EBV played any role in MS beyond the disease’s initiation. Thus, the lab decided to perform both in vitro and in vivo tests using MSRV and syncytin-1 to attempt to answer these questions more fully.
Based on a series of in vitro and in vivo tests, the lab was able to show several important things about EBV, MSRVenv, syncytin-1, and their relationships to MS. The most notable finding is that EBV does, in fact, activate the expression of HERV-W (specifically MSRVenv and syncytin-1) by astrocytes (glial cells).
Interactions between HERV-W and EBV in the in vitro experiments occur in cells from both the blood and the brain, which suggests that the same might be true for in vivo interactions. Based on this, the possibility that EBV activates HERV-W’s immunopathogenic and neuropathogenic potentials has become more than just a possibility. When EBV has progressed to IM in late adolescence or early adulthood, and thus become “superinfectious,” the possibility for these interactions could increase exponentially. This would more fully explain the link between EBV that causes IM (as opposed to other incidences of EBV) and MS.
What started as an improbable coincidence, then, has become a more cemented conclusion. Though EBV is incredibly common, EBV that progresses (often in late adolescence to early adulthood) to IM is less so, and the particulars of this research establish a definite link between this form of EBV and MS. Though the lab did not establish what role, if any, EBV could play in MS beyond the initiation of the disease, they did fully establish the link between EBV and MS. They also pointed out in the conclusions of their article that during revisions, their findings were independently verified by a multicentric study, making the results even more valid and important.
The medical community (and perhaps the CDC website) should thus reconsider their evaluation of EBV as mild and harmless, as MS can certainly not be described thus. It also raises questions about EBV: the CDC page expresses little concern over transmission of EBV (“transmission of the virus is almost impossible to prevent”), and offers few possibilities for treatment. It does, however, mention that a 5-day course of steroids may be prescribed to control swelling of the throat and tonsils. Since similar courses of steroids are often prescribed for MS patients following a flare-up to control inflammation of lesions, should it become common practice to prescribe steroids for all patients whose EBV has progressed to IM? Or, for possible MS prevention, would it be possible to prevent the interactions between EBV and HERV-W found in the study from ever occurring? Clearly, EBV in young adults that progresses to IM should be seen as a different and more serious medical situation than other EBV cases, and deserves further investigation and a more useful (and universal) course of treatment.
The paper summarized in this article:
Mameli G, Poddighe L, Mei A, Uleri E, Sotgiu S, et al. (2012) Expression and Activation by Epstein Barr Virus of Human Endogenous Retroviruses-W in
Blood Cells and Astrocytes: Inference for Multiple Sclerosis. PLoS ONE 7(9): e44991. doi:10.1371/journal.pone.0044991
Other sources cited (the footnotes didn’t copy-paste, so here’s my bibliography):
Laino, Charlene. “Epstein-Barr Virus Linked to MS.” WebMD. WebMD, 04 May 2009. Web. 01 Nov. 2012. <http://www.webmd.com/multiple-sclerosis/news/20090504/epstein-barr-virus-linked-to-ms?src=RSS_PUBLIC>.
“National Multiple Sclerosis Society.” FAQs about MS : National MS Society. N.p., n.d. Web. 01 Nov. 2012. <http://www.nationalmssociety.org/about-multiple-sclerosis/what-we-know-about-ms/faqs-about-ms/index.aspx>.
Hayes, Colleen E., Margherita T. Cantorna, and Hector F. DeLuca. “Experimental Biology and Medicine.” Vitamin D and Multiple Sclerosis. Experimental Biology and Medicine, Oct. 1997. Web. 01 Nov. 2012. <http://ebm.rsmjournals.com/content/216/1/21.short>.
“Epstein-Barr Virus and Infectious Mononucleosis.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 16 May 2006. Web. 01 Nov. 2012. <http://www.cdc.gov/ncidod/diseases/ebv.htm>.