Summary:
A new study from McMaster University shows that common respiratory infections — including influenza A and SARS-CoV-2 (the virus that causes COVID-19) — can accelerate the onset and functional decline of amyotrophic lateral sclerosis (ALS). In preclinical models, a single, sublethal respiratory infection triggered a long-lasting inflammatory response in the spinal cord (gliosis) that persisted after the virus was cleared from the lungs. Importantly, early antiviral treatment or targeted anti-inflammatory therapy reduced this post-infectious neuroinflammation and slowed the accelerated progression of ALS-like symptoms.
Key Facts:
- Infection accelerates motor decline: Animal models of ALS exposed to influenza A or SARS-CoV-2 developed significantly faster loss of motor function than uninfected controls.
- Persistent neuroinflammation without direct neural infection: Neither virus directly infected motor neurons. Instead, peripheral respiratory infection provoked a sustained spinal cord gliosis — increased activation of astrocytes and microglia — that remained elevated long after the respiratory infection resolved.
- Therapeutic reversibility: Administering antivirals to limit initial viral replication or using anti-inflammatory agents to resolve gliosis substantially blunted the infection-driven acceleration of disease.
Source: McMaster University
Overview of ALS and the study’s focus
Amyotrophic lateral sclerosis (ALS), often called Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disorder marked by the loss of upper and lower motor neurons. As these neurons deteriorate, patients experience muscle weakness, loss of mobility, progressive paralysis and ultimately respiratory failure. Epidemiological studies have long reported associations between various viral infections and increased risk or accelerated progression of neurodegenerative disease, but the biological mechanisms explaining those links remained unclear.
Researchers at McMaster University set out to define how common respiratory viruses influence ALS disease course. Instead of relying solely on population data, the team used mechanistic experiments in the SOD1G93A mouse model of ALS to test whether an acute, sublethal respiratory infection could alter the timing and severity of motor decline.
The investigators found that a single respiratory infection prior to clinical onset produced a measurable, lasting effect: infected animals showed a markedly more rapid deterioration in hindlimb function than uninfected controls. This accelerated decline occurred even though the viruses did not invade motor neurons in the brain or spinal cord.
Mechanism — the role of spinal cord gliosis
Detailed histological and molecular analyses identified the key mediator as neuroinflammation. Peripheral respiratory infection provoked a strong immune response that activated resident glial cells in the spinal cord — a process known as reactive gliosis. Both astrogliosis and microgliosis intensified and became entrenched after infection, producing a sustained inflammatory environment linked to neuronal dysfunction.
While reactive gliosis is already recognized as a hallmark of established ALS, this study shows that an unrelated peripheral infection can act as a catalyst, amplifying and prolonging that inflammatory state. Crucially, elevated gliosis in the lumbar spinal cord persisted long after the respiratory virus had been cleared from lung tissue, suggesting a durable change in the local neuroimmune milieu that promotes motor neuron vulnerability.
“ALS is a devastating and currently incurable disease, so it’s critical we better understand environmental factors that can hasten its onset and progression,” said Matthew Miller, Ph.D., the study’s principal investigator and a professor of biochemistry and biomedical sciences at McMaster. “Clarifying these triggers could reveal practical interventions to slow or prevent disease acceleration.”
Intervention strategies: antivirals and anti-inflammatories
The most actionable result from the study is that the infection-driven acceleration of ALS can be mitigated. The research evaluated two complementary pharmacological strategies:
- Early antiviral treatment: Administering direct-acting antiviral agents during acute infection reduced systemic viral load and substantially weakened the downstream acceleration of ALS-like symptoms.
- Anti-inflammatory therapy after infection: Using an anti-inflammatory small molecule to suppress and resolve spinal cord gliosis protected motor neurons and slowed functional decline, bringing outcomes closer to those of uninfected animals.
These findings suggest a practical clinical pathway: preventing or limiting common respiratory infections through vaccination or prompt antiviral therapy, and applying neuroprotective anti-inflammatory strategies after infection, may reduce the risk that such infections accelerate motor neuron disease in vulnerable individuals.
“Improved vaccination coverage and timely antiviral care could have protective benefits for the nervous system that are currently underappreciated,” Miller added. The study underscores the importance of seasonal vaccination, early medical treatment of respiratory infections, and further research into targeted anti-inflammatory approaches for people living with or genetically predisposed to ALS.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by staff.
About this ALS and virology research:
- Media Contact: Adam Ward
- Source: McMaster University
- Image Credit: Image credited to Neuroscience News
- Original Research is Open Access: Nature Communications (Sept 22, 2026). “Acute viral infection accelerates neurodegeneration in a mouse model of ALS.” Authors: Art Marzok, Jonathan P. Mapletoft, Imran Ahmed, Braeden Cowbrough, Daniel B. Celeste, Michael R. D’Agostino, Jann C. Ang, Andrew T. Chen, Vithushan Surendran, Yona Tugg, Hahn Li, Karena Wong, Anna Dvorkin-Gheva, Ali Zhang, Hannah D. Stacey, Mannie Lam, Yasmine Kollar, Kevin R. Milnes, Sam Afkhami & Matthew S. Miller.
- DOI: 10.1038/s41467-026-77353-y
Abstract
Acute viral infection accelerates neurodegeneration in a mouse model of ALS.
Several viral infections have been associated with amyotrophic lateral sclerosis (ALS), but the mechanisms by which they influence disease have been unclear. This study investigates the effect of common, acute respiratory viral infections on ALS onset and progression in the SOD1G93A mouse model. A single sublethal infection before clinical signs of ALS was associated with markedly accelerated disease progression, characterized by rapid loss of hindlimb function.
Prior infection produced gliosis in the lumbar spinal cord and upregulation of transcriptional pathways linked to inflammation, metabolic disruption and muscle dysfunction. Therapeutic suppression of gliosis with an anti-inflammatory small molecule, or treatment with a direct-acting antiviral, was associated with significantly improved clinical outcomes, resembling those seen in uninfected animals. These results provide causal, mechanistic evidence that the immune response to acute viral infections can be an important factor that alters ALS disease trajectory.