Study identifies the viral genetic pathways involved in different types of damage to the nervous system

New research led by Texas A&M University scientists shows that viral infections contribute to neurological diseases such as multiple sclerosis (MS) by triggering multiple pathways that damage the myelin sheath (the protective coating on nerve fibers, or axons) and the cells within those axons.

In addition, while this virus-induced axon damage is influenced by genetics, the genetic pathways are not necessarily the same for each affected individual.

“MS is complex because everyone has different symptoms and experiences, with some people recovering after a single incident, others steadily growing worse over time, and still others going through every possible scenario in between,” said Candice Brinkmeyer-Langford, PhD, a neurogenerative disease expert with the Texas A&M School of Public Health. “That makes it difficult to determine treatment or predict how someone with MS will fare.”

She said scientists use several different models to study specific aspects of MS, such as flare-ups or ongoing progression, and use genetically identical mice to ensure consistent results.

For their study, which was supported by the National Institutes of Health and published in a special issue of the International Journal of Molecular Sciences, the team used a common model that used a virus—Theiler’s murine encephalomyelitis virus (TMEV)—to trigger an immune response that mimics the link between a previous viral infection (like Epstein-Barr) and MS in humans.

“But instead of genetically identical mice, we used a diverse group that mirrored the genetic diversity found in humans to evaluate how genetic variety affects MS,” she said.

The team expanded the data from their previous study to include information for 15 different genetic strains that showed some damage in at least one area of the brain.

They then assessed them to find out which strains were susceptible to brain and spinal cord damage versus those that were not, regardless of any other health issues.

They found two specific genetic backgrounds where myelin loss developed through different genetic causes, indicating that this damage isn’t caused by a single, classic pathway, but by several different gene variations working together.

The researchers dubbed the results in these mice “axonal loss” to differentiate it from the type of damage to the myelin sheath typically seen in studies using genetically identical mice.

The findings suggest that both demyelinated strains have the same problem: an imbalance between the body’s ability to regenerate tissue and its response to infections.

In the CC002 strain, some repair mechanisms seemed to be active, partially counteracting the damage.

In contrast, the CC023 strain seemed to have its protective programs profoundly suppressed while stress signals in response to infection were exaggerated. This combination likely sped up nerve damage and recovery failure, reinforcing the idea that different genetic paths can lead to the same disease outcome.

“Based on these findings, we believe TMEV-infected CC002 and CC023 will be useful animal models for developing treatments for neurological disease, tailored to different patients’ unique genetic profiles,” Brinkmeyer-Langford said.

Others involved in the study were Colin R. Young, PhD, C. Jane Welsh, PhD, and graduate student Tae Wook Kang from Texas A&M’s College of Veterinary Medicine & Biomedical Sciences, and colleagues from Procter & Gamble and Colorado State University. Brinkmeyer-Langford and Welsh also are with the Texas A&M Institute for Neuroscience.