Tuesday, April 12, 2016

Mutant Viruses

As most people in the M.E. community know, there have been many red herrings and inconsistencies in the search for a specific viral trigger. Perhaps any one of several viruses can be a trigger in susceptible individuals - e.g. those of us with certain genetic polymorphisms, nutrient deficiencies, toxin exposure, chronic stress, PTSD, etc. It's also possible that some viruses may not always take their canonical form. Consequently standard antibody tests may not return conclusive results.

While parsing a paper on micronutrients, I came across an interesting passage:

A general overview of the roles of trace elements and immunity is incomplete without mention of the exciting discoveries by Beck and Levander. These investigators have shown that changes in the intracellular environment that are induced by alterations in micronutrient status can directly influence viral virulence and in addition can cause immune system dysfunction. The sentinel discovery is that selenium deficiency promotes the mutation of an avirulent strain of Coxsackie virus in the heart to a strain that causes myocarditis when the virus is passed from the selenium-deficient to a nutritionally adequate host (10). Because this modification of the viral genome also is observed in mice that are either deficient in vitamin E, overloaded with iron or lacking the glutathione peroxidase gene, it appears that the more oxidative intracellular environment that results from deficient or excess levels of some of the micronutrients promotes the genomic alteration that enhances virulence. The recent discovery that selenium deficiency also increases lung pathology in mice that are infected with influenza virus demonstrates that this effect is not limited to Coxsackie virus (11)

The paper that they refer to, by Beck and Levander, is an easy read (as medical papers go) and contains some brilliant detective work and beautifully orchestrated experiments. Check it out:

Selenium Deficiency and Viral Infection

In short, it was observed that Keshan disease was prevalent in areas of China with selenium-poor soil, and outbreaks followed a seasonal pattern, suggesting the involvement of a pathogen. An experiment with Selenium-deficient mice, and mice lacking the gene for glutathione peroxidase (a key enzyme in the antioxidant system) dovetailed with these findings. Most spectacularly, when healthy mice were injected with viral particles from Selenium-deficient mice, they developed the same pathology. The virus itself had changed!

The paper then explores some similar phenomena: mutations of the influenza virus in the presence of reactive oxygen species (ROS), and an outbreak of neuropathy in Cuba linked to nutrient deficiency, ROS, and viral mutation.

I did some preliminary searches of the literature for Epstein-Barr virus (EBV) mutations. EBV crops up frequently in theories of the etiology of M.E. Retrospectively, I've become suspicious that it had a roll in my development of fibromyalgia. I never had standard symptoms of Mononucleosis/Glandular Fever, but when my fibro symptoms first kicked off I had a nasty case of pinkeye. It was stubborn; after 2 years, a dozen ophthalmology/optometry visits, and numerous antibiotic drops, all it did was switch eyes. To this day, I still have a drooping eyelid, inflamed lid margins, light sensitivity, and a patchy tearfilm, but the worst of the pinkeye was cleared up by a few drops of colloidal silver. Those antibiotics hadn't worked because I did not have a bacterial infection. I had a viral one, perhaps EBV.

Anyway, to the literature search! This is just the tip of the iceburg, I'm sure. I wish I had more time and energy, but even a healthy person cannot sift through the 2.5 million studies on PubMed.

Well, well:
A comprehensive library of mutations of Epstein Barr virus.

An Epstein-Barr Virus (EBV) mutant with enhanced BZLF1 expression causes lymphomas with abortive lytic EBV infection in a humanized mouse model.

Reactive oxygen species mediate Epstein-Barr virus reactivation by N-methyl-N'-nitro-N-nitrosoguanidine.

When it comes to EBV, there's a lot to study. In future posts I'd like to discuss its effect on the Vitamin D receptor (VDR) and on cytokine expression.

There also, surely, is literature on mutations among other viruses of note. Go forth and trawl PubMed!

Other Sources:

Trace Elements and Host Defense: Recent Advances and Continuing Challenges

Selenium Deficiency and Viral Infection

1 comment:

  1. This related read looks promising too:
    "Mechanisms of restriction of viral neuroinvasion at the blood-brain barrier."