Viral Infections and Autoimmunity in Multiple Sclerosis

Multiple sclerosis (MS) is characterised by immune-mediated demyelination and neurodegeneration within the central nervous system. Although genetic predisposition and environmental factors both contribute to disease onset and progression, persistent viral infections have emerged as key modulators of MS risk and activity. Viruses such as Epstein–Barr virus (EBV), human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) establish lifelong latency and periodically reactivate, driving chronic inflammation and the release of self-antigens. Reactivation events may provoke autoreactive T-cell expansion through mechanisms including molecular mimicry, bystander activation and epitope spreading. Elevated levels of neurofilament light chain, a marker of axonal injury, often coincide with viral seroconversion or increased viral load, suggesting that subclinical viral activity may precipitate neuronal damage long before clinical presentation. Understanding the interplay between latent viral reservoirs, adaptive immune responses and genetic susceptibility loci is critical for the development of targeted antiviral or immunomodulatory therapies in MS.

Research from Nature Portfolio

Studies have demonstrated that CMV infection influences the pool of cytotoxic CD4+CD28null T cells, which expand in CMV-seropositive individuals and infiltrate demyelinated regions of the spinal cord. In experimental autoimmune encephalomyelitis (EAE), prior CMV exposure intensified disease severity by augmenting autoreactive T-cell responses against myelin antigens and increasing demyelination. These findings indicate that CMV-driven T-cell subsets may act as amplifiers of CNS autoimmunity and represent a potential target for therapeutic intervention.

Viral Infections and Autoimmunity in Multiple Sclerosis publication trend

The graph below shows the total number of articles in viral infections and autoimmunity in multiple sclerosis across all publications each year (not limited to Nature Index journals).

Technical terms

Autoimmunity: Immune response directed against the body’s own tissues.

Demyelination: Loss or damage of the myelin sheath surrounding nerve fibres in the CNS.

Neurofilament light chain: A structural neuronal protein released into biofluids upon axonal injury.

Seropositivity: Presence of specific antibodies in the blood indicating prior exposure or infection.

Latent infection: Dormant state of a virus within host cells, capable of reactivation.

Molecular mimicry: Immune cross-reactivity triggered by similarity between viral and self-antigens.

References

1. Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis. Brain (2023).
2. Risk of a first clinical diagnosis of central nervous system demyelination in relation to human herpesviruses in the context of Epstein–Barr virus. European Journal of Neurology (2023).
3. Role of Viruses in the Pathogenesis of Multiple Sclerosis. Viruses (2020).
4. Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation. Scientific Reports (2017).