Nav: Home

Are the 'viral' agents of MS, ALS and schizophrenia buried in our genome?

July 11, 2019

What if the missing 'environmental' factor in some of our deadliest neurological diseases were really written in our genome?

Writing in Frontiers in Genetics, researchers from the University of Dusseldorf explain how viruses ended up in our DNA - and what puts them in the frame in unsolved diseases like multiple sclerosis.

The enemy within

A whopping 8% of our DNA comes from viruses. Specifically, ones called retroviruses - not because they're old, but because they reverse the normal process of reading DNA to write themselves into their host's genome.

Retroviruses are old though: they began merging with our earliest, primordial ancestors millions of years ago. Over the millennia, most of their remnants in our DNA - known as human endogenous retroviruses or HERVs - have been silenced by mutations. Others, which had evolved to fend off rival viruses, formed the prototypical immune system and to this day protect us from infection.

However, HERVs might also be the missing causative link in major 'unsolved' neurological diseases.

"HERVs have been implicated in the onset and progression of multiple sclerosis [MS], amyotrophic lateral sclerosis [ALS] and schizophrenia [SCZ]," says senior author Prof. Patrick Kuery. "Dormant HERVs can be reactivated by environmental factors such as inflammation, mutations, drugs, or infection with other viruses, so could provide a mechanism for their well-established epidemiological link to these disorders."

Role in MS

So far, the strongest evidence links HERVs to MS.

"MS is caused by direct autoimmune attacks on myelin - the fatty coating of nerve cells - in the brain and spinal cord," explains Kuery. "But we don't yet understand how these attacks are triggered."

A variety of studies suggest that reactivation of HERV could be just such a trigger.

"Retroviruses were first associated with MS in 1989, but only decades later was it realized that these are in fact HERVs.

"Subsequently, it was shown that levels of HERV RNA and protein - the 'readouts' from reactivated HERV DNA - are increased in the brain and spinal cord fluid [CSF] of sufferers, as well as in their brain tissue postmortem.

"Linking this HERV reactivation to autoimmune attacks in MS, it was found that HERV proteins can trigger an immune response against myelin, which triggers MS-like disease in mouse models."

Mechanistically, HERV proteins could trigger autoimmunity through 'molecular mimicry'.

"In addition to direct effects of HERV on myelinating cells, several groups report structural similarities between HERV and myelin oligodendrocyte glycoprotein - a molecule displayed on the surface of myelin. This similarity could fool the immune system into damaging myelin, when it mounts an attack on HERVs."

Experimental proof in humans

Similar experiments have linked HERVs to the peripheral demyelinating disease CIDP, as well as more distinct disease processes like progressive loss of motor neurons in ALS (Lou Gehrig's disease).

In schizophrenia, a complex neurodevelopmental disorder, the link to HERVs is more circumstantial.

"HERV proteins have been reported to increase expression of schizophrenia-linked genes in cultured human brain cells," reports Kuery. "However, studies on schizophrenia sufferers show inconsistent changes in HERV expression in blood, CSF and postmortem brain tissue compared to healthy controls."

Whether or not HERVs contribute to these and other unexplained neurological conditions requires further investigation. An important step will be to test the effects of HERV-neutralizing antibodies in humans.

"Of note, in relapsing MS patients a phase 2b clinical trial using HERV protein-neutralizing antibody Temelimab has been conducted. We're now waiting to see if the treatment showed beneficial effects on remyelination or attenuated neurodegeneration," Kuery concludes.
-end-
Please link to the original research article in your reporting: https://www.frontiersin.org/articles/10.3389/fgene.2019.00655/full

Frontiers is an award-winning Open Science platform and leading open-access scholarly publisher. Our mission is to make high-quality, peer-reviewed research articles rapidly and freely available to everybody in the world, thereby accelerating scientific and technological innovation, societal progress and economic growth. Frontiers received the 2014 ALPSP Gold Award for Innovation in Publishing. For more information, visit http://www.frontiersin.org and follow @Frontiersin on Twitter.

Frontiers

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#530 Why Aren't We Dead Yet?
We only notice our immune systems when they aren't working properly, or when they're under attack. How does our immune system understand what bits of us are us, and what bits are invading germs and viruses? How different are human immune systems from the immune systems of other creatures? And is the immune system so often the target of sketchy medical advice? Those questions and more, this week in our conversation with author Idan Ben-Barak about his book "Why Aren't We Dead Yet?: The Survivor’s Guide to the Immune System".