Summary:
A new study from McMaster University reveals that common respiratory infections, such as influenza A and COVID-19, accelerate the onset and functional decline of amyotrophic lateral sclerosis (ALS). Even without directly infecting neurons, a single viral bout triggers sustained, chronic gliosis in the spinal cord that persists long after the virus clears. Crucially, treating infections with antivirals or quelling inflammation with anti-inflammatory compounds significantly slowed disease progression in preclinical models.
Key Facts:
- Infection Accelerates Motor Decline: Preclinical animal models of ALS exposed to either influenza A or SARS-CoV-2 experienced significantly faster loss of motor function compared to uninfected controls.
- Persistent Neuroinflammation Without Direct Neural Infection: The respiratory viruses did not directly infect motor neurons; instead, the systemic immune response sparked prolonged spinal cord gliosis (glial scarring and inflammation) that remained elevated long after the viral infection resolved.
- Therapeutic Reversibility: Administering antiviral agents to limit the initial infection or deploying anti-inflammatory drugs to suppress post-viral gliosis substantially blunted the accelerated rate of ALS progression.
Source: McMaster University
Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease, is a devastating and fatal neurodegenerative disorder characterized by the progressive death of upper and lower motor neurons. As these essential conduits between the central nervous system and skeletal muscles degrade, patients experience muscle atrophy, loss of mobility, progressive paralysis, and eventual respiratory failure.
While epidemiological studies have long noted statistical correlations between diverse viral infections and heightened risks for neurodegenerative conditions, a central biological paradox remained unresolved: How could a disparate array of common viruses, most of which never cross into neural tissue, produce a similar accelerated pattern of motor neuron decline?
Now, a study led by researchers at McMaster University and published in Nature Communications provides the mechanistic answer. The investigators demonstrated that common respiratory viruses alter the course of ALS not through direct viral neurotropism, but through the long-tail inflammatory response mounted by the immune system.
“ALS is a debilitating and incurable disease, so it’s critical that we improve our understanding of the common environmental factors that can hasten its onset and accelerate its progression,” said principal investigator Matthew Miller, Ph.D., a professor of biochemistry and biomedical sciences at McMaster, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research, and executive director of NexusHealth. “Understanding what triggers or accelerates the disease could illuminate new strategies for slowing or even stopping it.”
A Single Respiratory Infection Accelerates Functional Decline
To examine how respiratory pathogens interface with motor neuron biology, the researchers monitored animal models of ALS following acute infection with either influenza A virus or SARS-CoV-2 (the causative agent of COVID-19). They tracked disease trajectories alongside an uninfected control cohort.
The animals that contracted viral infections suffered a markedly more rapid deterioration in motor performance than their uninfected counterparts.
“A lot of the previous work in this area has been epidemiological in nature, without much focus on the molecular mechanisms that actually underpin the connection between infections and ALS,” said co-first author Imran Ahmed, a master’s student in the Miller laboratory who co-led the study alongside lab alumni Art Marzok, Ph.D., and Jonathan Mapletoft, Ph.D. “What makes our study unique is that we did take a mechanistic approach — we explored why this connection might exist.”
The Fuel Behind the Fire: Spinal Cord Gliosis
Histological and molecular analyses revealed that neither the flu virus nor the coronavirus directly infected neurons in the brain or spinal cord. Instead, the peripheral respiratory insult triggered a profound inflammatory reaction by the nervous system’s resident immune cells, a reactive cellular response known as gliosis.
While reactive astrogliosis and microgliosis are recognized hallmarks of established ALS pathology, the research team discovered that a single viral infection acts as a physiological catalyst, dramatically amplifying and entrenching this neuroinflammatory state. Most importantly, reactive gliosis remained locked at high levels in the spinal cord well after the respiratory virus had been cleared from peripheral lung tissue.
“In our pre-clinical models, just one viral infection was enough to significantly accelerate ALS progression, even after the infection itself had resolved,” said Dr. Marzok. “These findings strongly suggest that viral infections, and the inflammatory responses that they trigger, may fundamentally influence the course of the disease.”
Antivirals and Anti-Inflammatories Offer Neuroprotection
The study’s most actionable discovery lies in disease intervention. Because ALS currently lacks a cure, preventing or mitigating environmental accelerators represents a practical clinical frontier.
During the study, Miller’s team evaluated two distinct pharmacological strategies:
- Early Antiviral Intervention: Treating acute viral infections early with targeted antivirals minimized systemic viral load and substantially suppressed downstream ALS acceleration.
- Post-Infection Anti-Inflammatory Therapy: Deploying anti-inflammatory compounds to specifically block and resolve spinal gliosis shielded motor neurons and significantly slowed functional motor decline.
“Developing better vaccines and antiviral therapies, and improving the public’s trust in them, could have health benefits that we don’t fully appreciate,” Miller emphasized. “Our work here suggests that preventing or limiting common infections could at the same time protect your nervous system from the damage that accelerates ALS.”
The findings underscore the importance of seasonal vaccinations, prompt antiviral treatment, and anti-inflammatory neuroprotective strategies for individuals living with, or genetically predisposed to, motor neuron disease.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our 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.
While several viral infections have been associated with amyotrophic lateral sclerosis (ALS), the mechanism(s) through which they promote disease remains elusive.
Here we investigate the impact of common, acute viral infections on ALS disease onset and progression in the SOD1G93A mouse model. A single sublethal infection prior to onset of ALS clinical signs is associated with markedly accelerated ALS disease progression characterized by rapid loss of hindlimb function.
Prior infection results in gliosis in the lumbar spine and upregulation of transcriptional pathways involved in inflammatory responses, metabolic dysregulation, and muscular dysfunction. Therapeutic suppression of gliosis with an anti-inflammatory small molecule, or administration of a direct-acting antiviral, is associated with significantly improved ALS clinical signs, akin to what is observed in uninfected animals.
Our study provides causal and mechanistic evidence that the immune response elicited by acute viral infections may be an important etiological factor that alters ALS disease trajectory.
