Dormant Viruses In Our Genome Can Damage Brain Development If Activated

Human endogenous retroviruses can disrupt brain development if they get activated. Image Credit: Giovanni Cancemi/Shutterstock.com

A new study, led by researchers from Helmholtz Zentrum München and published in the journal Cell Stem Cell, has for the first time shown that dormant human endogenous retroviruses, known as HERVs, can impair neural development if artificially activated in human embryonic pluripotent stem cells. 

HERVs are remnants of ancient viruses that infected our ancestors and over time these elements embedded themselves within the human genome. Although HERVs lost their ability to self-replicate and infect as part of evolution, they do form an important part of our genetic makeup and are especially abundant in non-coding regions of our DNA.  

"We have carried these elements for about 40 to 70 million years. We assume that their presence is relevant to our natural processes, otherwise we would not have retained them for so long during evolution,” said Dr. Michelle Vincendeau in a statement.

While some HERVs are active and can influence the expression of other genes in humans, other remnants remain dormant until they are activated by external factors such as bacterial infections, UV light, or other viruses that make it into cells.

Studies have linked HERV elements to an array of biological processes, including placental development and the ability of embryonic pluripotent stem cells to develop into other cell lineages. HERVs have also been linked to different disease onsets such as cancer, when activated in humans, however, our full understanding of these endogenous elements remains obscured. 

Now, researchers led by Dr Vincendeau have shown, with the use of a CRISPR gene technology tool, that the activation of a specific HERV named HERV-K(HML-2) element in human pluripotent stem cells leads to the impairment of neuronal cells that would normally differentiate into cortical neurons of the brain. 

The study activated the HERV-K(HML-2) element during different stages of pluripotent stem cell differentiation, which caused cortical neurons not to develop as they should and resulted in the brain cells losing their function entirely. This was the first time a negative impact associated with the specific activation of a HERV during brain development had been demonstrated.

"I think our study shows that reactivation of these elements can have a negative impact on brain development. Thus, if these elements get reactivated by environmental factors they might have the potential to drive neurodegenerative diseases or neurological diseases."  Dr Vincendeau explained to IFLScience by email. 

For the next steps, Dr Vincendeau and the team want to continue their investigation into the role of HERV activation. Are there specific stages that these HERV's are activated during normal brain development, and what is it that regulates this process? 

"Thus, we now want to move on and have a look, which exact functional role do such elements take over in brain cells. Moreover, we also want to better understand how they are regulated in different brain cell types and at different brain developmental stages. Only with these data we will be able to better understand their potential influence on neurodegenerative diseases like Alzheimer’s disease, Parkinson's disease and evaluate if these elements are a good treatment target,"  Dr Vincendeau concluded. 


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