Ancient viral DNA in the human genome linked to multiple sclerosis and amyotrophic lateral sclerosis

New research from King’s College London has revealed a link between ancient viral DNA embedded in the human genome and the genetic risk of two major diseases that affect the central nervous system.

The study, led by researchers from King’s College London and Northwell Health, focused on human endogenous retroviruses (HERVs), remnants of ancient retroviral infections that are now fixed features in our DNA. Using a cutting-edge genomic technique, the team identified specific HERV expression signatures linked to multiple sclerosis and amyotrophic lateral sclerosis (also known as motor neuron disease). These results suggest that viral elements present in our DNA could play a role in the development of these neurodegenerative diseases.

Neurodegenerative diseases are characterized by progressive degeneration and loss of neurons, leading to deterioration in the structure and function of the nervous system. Multiple sclerosis is one of the most common neurodegenerative diseases among young adults, with more than 150,000 people in the UK living with the condition for life. Amyotrophic lateral sclerosis is less common, with around 5,000 cases in the UK, and is associated with a worse prognosis.

Published in Brain, behavior and immunitythe study marks an important advance in understanding the complex genetic architecture of neurodegenerative diseases. While previous studies have hinted at a link between HERVs and these conditions, this one is among the first to identify specific HERVs associated with disease susceptibility.

“Our results offer strong evidence that specific viral sequences within our genome contribute to the risk of neurodegenerative diseases,” said Dr. Rodrigo RR Duarte, co-senior author of the study and researcher at the Institute of Psychiatry and of psychology (IoPPN). King’s College London. “These sequences are not just static fossils derived from ancient viral infections: they must actively influence brain function in ways that we are only beginning to understand.”

Researchers analyzed data from hundreds of brain samples to map the relationship between HERV expression and genetic risk factors for four neurodegenerative diseases: Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis.

They identified a robust HERV signature on chromosome 12q14 (MER61_12q14.2) associated with amyotrophic lateral sclerosis, and another on chromosome 1p36 (ERVLE_1p36.32a), associated with multiple sclerosis. These viral sequences appear to be involved in homophilic cell adhesion, a process essential for communication between brain cells. No robust signatures were observed for Alzheimer’s and Parkinson’s diseases, although the authors point out that larger studies may uncover new associations in the future.

As the global burden of neurodegenerative diseases continues to grow – with more than 50 million people currently affected worldwide, a number expected to nearly triple by 2050 – this information offers a promising direction for future research and development. treatments. This discovery opens new possibilities for therapeutic interventions targeting HERVs. By better understanding how these viral elements drive disease, researchers hope it could contribute to the development of new treatments that could lessen the impact of neurodegenerative diseases.

“Using large genetic datasets and a novel analysis pipeline, this study is well equipped to identify which specific HERVs are important for increasing susceptibility to neurodegenerative diseases,” said co-author Dr. Timothy R. Powell. Principal and Senior Lecturer in Translational Genetics and Neuroscience at King’s IoPPN.

“We now need to better understand the impact of these HERVs on brain function and whether or not targeting HERVs could provide new therapeutic opportunities.”