A new study has been able to prove for the first time that the activation of different endogenous human retroviruses, which are part of our genome, significantly impairs brain development.
The findings of the study, which emerged from an international collaboration led by researchers at Helmholtz Zentrum Munchen – German Research Center for Environmental Health, could help advance research into therapies for neurodegenerative diseases.
Since our ancestors became infected with retroviruses millions of years ago, we have carried elements of these viruses into our genes – known as human endogenous retroviruses, or HERV for short, the researchers said.
These viral elements have lost their ability to replicate and infect during evolution, but are an integral part of our genetic makeup. In fact, humans have five times more HERV in non-coding parts than coding genes. So far, special attention has been paid to the correlation of HERVs and the onset or progression of disease.
Therefore, the expression of HERV was studied in samples of pathological origin. Although important, these studies do not provide conclusions as to whether HERVs are the cause or consequence of such disease.
Today, new technologies allow scientists to better understand the mechanisms of HERVs and their function. Together with her colleagues, virologist Michelle Vincendeau * succeeded for the first time in demonstrating the negative effects of HERV activation on human brain development.
Using CRISPR technology, the researchers activated a specific group of endogenous human retroviruses in human embryonic stem cells and generated nerve cells (neurons).
These viral elements in turn activated specific genes, including classic developmental factors, involved in brain development. As a result, cortical neurons, that is, nerve cells in our cerebral cortex, have completely lost their function.
They developed very differently from healthy neurons in this region of the brain – with a much shorter axon (extension of nerve cells) that was much less branched. Thus, activation of a specific HERV group impairs the development of cortical neurons and ultimately brain development.
Since neurodegenerative diseases are often associated with the activation of multiple HERV groups, the negative impact of HERV activation on the development of cortical neurons is a key finding.
It is already known that environmental factors such as viruses, bacteria and UV light can activate distinct HERVs, thus potentially contributing to the onset of disease. This knowledge, in turn, makes HERVs even more attractive for clinical application. The deactivation of distinct viral elements could open a new field of research for the treatment of patients with neurodegenerative diseases.
In the next step, Helmholtz Zentrum Munchen’s group will study the impact of deactivation of HERV in neurons in the context of the disease.
In addition, research results provide important indications that epigenetic mechanisms keep viral elements under control in healthy brain development. Michelle Vincendeau even suspects a functional role of controlled HERVs in normal brain development.
“We have been transporting 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 kept them for so long during evolution,” explains Vincendeau. Further fundamental research in this direction could reveal new functional roles for HERVs.