Breakthrough study links ancient viral DNA to multiple sclerosis

Ancient viral DNA embedded in human genomes links to risks for neurodegenerative diseases like ALS and MS, offering hope for new therapies.

New research uncovers how ancient viral DNA in human genomes contributes to risks for ALS and MS, revealing novel therapeutic opportunities. (CREDIT: CC BY-SA 4.0)

Ancient viral DNA embedded in the human genome has been linked to the genetic risks of certain neurodegenerative diseases, according to groundbreaking research.

Human endogenous retroviruses (HERVs) are remnants of infections from ancient retroviruses that have integrated into our DNA. These sequences, which make up about 8% of the human genome, have been largely considered regulatory but can influence immune responses, cellular processes, and possibly, disease progression.

New research from King’s College London and Northwell Health has revealed specific HERV expression signatures associated with multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS), also known as motor neurone disease.

Published in the journal, Brain Behavior and Immunity, these findings provide valuable insights into the genetic underpinnings of these conditions and could open new doors for treatment development.

HERVs are ancient sequences that once operated as active viral genes. Though largely dormant, some HERVs retain the ability to produce non-coding RNAs and proteins.

Human endogenous retroviruses (HERVs) are remnants of infections from ancient retroviruses that have integrated into our DNA. (CREDIT: CC BY-SA 4.0)

These elements can trigger immune system responses through mechanisms such as the cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway, potentially leading to inflammation and other immune-related effects. They’ve also been linked to essential biological processes like placenta formation and cell fate determination.

Past studies have found abnormal HERV expression in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), ALS, and MS. However, pinpointing whether HERVs directly contribute to disease or merely correlate with symptoms has proven challenging.

Using a retrotranscriptome-wide association study (rTWAS) framework, the researchers aimed to identify HERVs genuinely involved in the aetiology of these conditions. This approach integrates genome-wide association study (GWAS) data with expression quantitative trait loci (eQTL) databases, allowing precise analysis of HERV expression in specific tissues, such as the brain.

HERVs are not merely genetic relics. Their activity has functional implications for immune response and neuroinflammation. This study’s findings underline the importance of exploring how these sequences influence brain function and contribute to disease pathways.

The study analyzed data from large-scale GWAS datasets, focusing on individuals of European ancestry. For ALS, Parkinson’s disease, Alzheimer’s disease, and multiple sclerosis, the researchers examined genetic variants associated with disease susceptibility and their impact on cortical HERV expression. In total, the study evaluated thousands of single nucleotide polymorphisms (SNPs) across genomic regions linked to these diseases.

Key findings included a robust association between HERV expression and MS and ALS susceptibility. In MS, a specific HERV sequence located on chromosome 1p36 (ERVLE_1p36.32a) was identified as downregulated in individuals at risk. For ALS, a sequence on chromosome 12q14 (MER61_12q14.2) was similarly linked. Both sequences were involved in homophilic cell adhesion, a critical process for brain cell communication.

Interestingly, the study did not find robust HERV signatures for Alzheimer’s and Parkinson’s disease, although researchers suggest that larger datasets may uncover additional links in the future. The variation in findings highlights the complex nature of genetic risks and the necessity for further research.

The implications of these findings extend far beyond genetic associations. “Our results offer robust evidence that specific viral sequences within our genome contribute to the risk of neurodegenerative diseases,” said Dr. Rodrigo R. R. Duarte, a lead author and research fellow at King’s College London. “These sequences are not just static fossils—they must be actively influencing brain function in ways we are only beginning to understand.”

Retrotranscriptome-wide association studies of neurodegenerative diseases. (CREDIT: Brain Behavior and Immunity)

The identified HERV sequences highlight novel biological mechanisms underlying MS and ALS. By better understanding these processes, researchers hope to develop therapeutic interventions targeting HERV activity. This approach could mitigate the progression or onset of these diseases.

HERV-targeted therapies could revolutionize treatment for neurodegenerative diseases, offering new hope for conditions that currently have limited options. Drugs or genetic interventions designed to modulate HERV activity might alleviate symptoms or slow disease progression, significantly improving patients' quality of life.

Neurodegenerative diseases are characterized by the gradual deterioration of neurons, leading to functional and structural damage in the nervous system. MS, one of the most common neurodegenerative conditions among young adults, affects over 150,000 people in the UK. ALS, while less prevalent, is known for its devastating impact, with around 5,000 cases in the UK and no cure currently available.

The global burden of neurodegenerative diseases continues to rise. Worldwide, over 50 million people are currently affected by these conditions, and this number is projected to nearly triple by 2050. These diseases not only impose significant challenges for individuals and families but also create substantial economic and healthcare burdens.

Conditional and joint analyses, and fine-mapping results. (CREDIT: Brain Behavior and Immunity)

Identifying genetic and environmental factors contributing to these diseases remains a critical area of research. This study’s findings contribute to the growing body of evidence that ancient viral sequences play a role in modern disease processes.

The research team emphasized the importance of expanding the scope of future studies. Dr. Timothy R. Powell, co-lead author and senior lecturer at King’s College London, noted, “Using large genetic datasets and a new analysis pipeline, this study is well-equipped to pinpoint which specific HERVs are important in increasing susceptibility to neurodegenerative diseases. We now need to better understand how these HERVs impact brain function and whether targeting them could offer therapeutic opportunities.”

The study’s authors also highlighted the challenges of interpreting genetic signals, particularly those originating from the major histocompatibility complex (MHC) locus. The complex linkage disequilibrium structure in this genomic region requires careful analysis to differentiate causal mechanisms from confounding factors.

By integrating additional data from diverse populations and applying advanced fine-mapping techniques, researchers hope to refine their understanding of HERV’s role in neurodegeneration. Collaborative efforts across disciplines and institutions will be crucial to translating these findings into clinical applications.

Future research may also explore the potential for HERVs to act as biomarkers for early diagnosis. Identifying HERV-related expression patterns in blood or cerebrospinal fluid could aid in detecting diseases before symptoms emerge, enabling earlier and more effective intervention.

Dr. Timothy R. Powell, co-lead author and senior lecturer at King’s College London. (CREDIT: Brain Behavior and Immunity)

The discovery of HERV signatures associated with MS and ALS provides a glimpse into how ancient viral DNA may influence modern health. These findings not only expand the understanding of genetic risk factors but also offer hope for novel treatment strategies targeting HERV activity. As research progresses, the potential to mitigate the burden of neurodegenerative diseases becomes increasingly tangible.

The ongoing investigation into HERVs underscores the interconnectedness of ancient and modern biology. By harnessing cutting-edge genomic tools and collaborative research efforts, scientists can continue uncovering the secrets embedded in our DNA, transforming insights into actionable treatments.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.


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Joshua Shavit
Joshua ShavitScience and Good News Writer
Joshua Shavit is a bright and enthusiastic 18-year-old with a passion for sharing positive stories that uplift and inspire. With a flair for writing and a deep appreciation for the beauty of human kindness, Joshua has embarked on a journey to spotlight the good news that happens around the world daily. His youthful perspective and genuine interest in spreading positivity make him a promising writer and co-founder at The Brighter Side of News. He is currently working towards a Bachelor of Science in Business Administration at the University of California, Berkeley.