Summary: New research links ancient viral DNA embedded in the human genome—known as human endogenous retroviruses (HERVs)—to genetic risk for two major neurodegenerative disorders: amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). By analysing hundreds of brain samples with advanced genomic methods, researchers identified specific HERV expression signatures associated with disease susceptibility, revealing potential genetic mechanisms and pointing toward new therapeutic targets.
Researchers from King’s College London and Northwell Health used a retrotranscriptome-wide association study (rTWAS) to map HERV expression in cortical brain tissue and relate it to genetic risk for several neurodegenerative diseases. Their findings, published in Brain, Behavior, and Immunity, provide robust evidence that particular HERVs contribute to ALS and MS risk, and help clarify how ancient viral elements in our DNA may influence brain function and disease.
Key Facts:
- Human endogenous retroviruses (HERVs) — remnants of ancient viral infections — are linked to increased genetic risk for ALS and MS.
- The study pinpointed distinct HERV expression signatures: MER61_12q14.2 for ALS and ERVLE_1p36.32a for MS.
- These HERVs appear connected to cellular adhesion processes in the brain and may represent novel therapeutic targets.
Source: King’s College London
Human endogenous retroviruses are sequences from ancient retroviral infections that became fixed in the human genome across evolutionary time. Although often described as genomic “fossils,” HERVs can be transcribed and may influence nearby genes or cellular processes. This study leveraged genomic precision to quantify HERV expression across 792 cortical samples, then integrated those expression models with large-scale genetic association data for Alzheimer’s disease, Parkinson’s disease, ALS and MS.
The analysis identified twelve HERV expression signatures linked to neurodegenerative disease susceptibility, with two showing particularly robust associations after rigorous statistical tests and fine-mapping. A HERV on chromosome 12q14 (MER61_12q14.2) was strongly associated with ALS, while a HERV on chromosome 1p36 (ERVLE_1p36.32a) was strongly associated with MS. Co-expression analyses suggest these HERVs may influence homophilic cell adhesion—interactions between identical adhesion molecules on neighboring cells that are critical for neuronal connectivity and signalling.
No similarly robust HERV signatures were observed for Alzheimer’s disease or Parkinson’s disease in this dataset, although the authors note that larger studies or additional brain regions could reveal further associations. The current results nonetheless highlight how specific viral-derived genomic elements can shape disease risk in a tissue-relevant context—here, the cortex—providing mechanistic clues that go beyond association alone.
Neurodegenerative diseases progressively damage neurons and neural circuits, producing lasting deficits in movement, cognition and quality of life. Multiple sclerosis commonly affects young adults, with over 150,000 people living with MS in the UK. Amyotrophic lateral sclerosis is less common—approximately 5,000 cases in the UK—but typically carries a more severe prognosis. Globally, more than 50 million people are currently affected by neurodegenerative disorders, and that number is expected to rise substantially by mid-century, underscoring the need for new mechanistic insights and therapies.
Co-lead authors Dr. Rodrigo R. R. Duarte and Dr. Timothy R. Powell emphasised that these HERV sequences are not merely genomic relics but may actively influence brain biology in ways that increase disease susceptibility. The study combined large genetic datasets with a novel analytical pipeline to isolate which HERVs are most likely to matter for disease risk, setting the stage for laboratory studies to test causal mechanisms and for translational work exploring whether targeting HERV activity could be therapeutically beneficial.
The research was part-funded by the NIHR Maudsley Biomedical Research Centre, the US National Institutes of Health (NIH), and The Psychiatry Research Trust. The study represents an important advance in the genetics of neurodegeneration by identifying concrete HERV candidates for follow-up, framing new experimental questions about how ancient viral DNA contributes to modern human disease.
About this neurology and genetics research news
Author: Franca Davenport
Source: King’s College London
Contact: Franca Davenport – King’s College London
Image: The image is credited to Neuroscience News
Original Research: Open access. “Ancient viral DNA in the human genome linked to neurodegenerative diseases” by Rodrigo R. R. Duarte et al., published in Brain, Behavior, and Immunity.
Abstract
Ancient viral DNA in the human genome linked to neurodegenerative diseases
Background
Human endogenous retroviruses (HERVs) are genomic segments derived from ancient retrovirus infections. Prior research has suggested links between HERVs and neurodegenerative disease, but connecting specific HERV elements to disease risk has been challenging. This study applied a retrotranscriptome-wide association study (rTWAS) framework to map HERV expression in the brain and assess relationships between HERV activity and genetic susceptibility for several neurodegenerative disorders.
Methods
The team analysed genetic association data for Alzheimer’s disease, amyotrophic lateral sclerosis, multiple sclerosis and Parkinson’s disease alongside HERV expression models built from 792 cortical brain samples. They applied strict significance thresholds, conditional and joint analyses, and fine-mapping procedures to identify robust HERV signatures linked to disease susceptibility.
Results
The primary analysis produced twelve HERV expression signatures associated with neurodegenerative disease risk. Two signatures met robust criteria: MER61_12q14.2 for ALS and ERVLE_1p36.32a for MS. Co-expression patterns implicate these HERVs in homophilic cell adhesion via plasma membrane adhesion molecules, a process relevant to neuronal communication and wiring.
Conclusions
This study identified distinct HERV expression profiles that are robustly associated with ALS and MS susceptibility, revealing novel genetic mechanisms and highlighting HERVs as potential targets for future therapeutic research in neurodegenerative disease.