Uncovering a potential link between oral herpes, multiple sclerosis

Two out of every three adults carry the herpes simplex virus type 1 that causes oral herpes, commonly recognized as cold sores. Subtle and largely asymptomatic, the virus can linger in the body, undetected, for a lifetime. For immunocompromised people, the risks are greater. 

“If you are infected, then your immune system is constantly locked in battle with the virus,” said Deepak Shukla, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye and professor of microbiology and immunology. “And if for any reason you become immunocompromised, the virus can escape and damage your brain.” 

In a new study, Shukla and colleagues in the College of Medicine describe a pathway linking herpes simplex virus type 1, or HSV-1, to a multiple sclerosis-like disease in animal models. Their research could improve the understanding, treatment and prevention of multiple sclerosis and other neurodegenerative diseases. 

The virus enters the body through the eyes and mouth and carries many potential threats, said Shukla, who recently linked the virus to anxiety, motor impairment and memory decline. Researchers have long suspected HSV-1 plays a role in neurodegenerative diseases, but the chemistry driving this connection is not fully understood.  

In 2021, Shukla’s team found that animals lacking the healing protein optineurin were at higher risk for HSV-1 infection, implicating one perpetrator in the herpes-to-neuronal-damage pipeline. 

Their new study, published in Clinical and Translational Medicine, introduces a second character to the campaign: the executioner proteins known as mixed lineage kinase domain-like proteins. These proteins oversee controlled cell death, often with inflammatory side effects. 

With this information, the researchers proposed a new pathway. 

Suppose a person carries the HSV-1 virus. If they are deficient in the healer protein, optineurin, that triggers a spike in the executioner protein. The protein then kills oligodendrocytes, which make armor, also known as myelin, that protects our neurons. Without myelin production, the nervous system is left vulnerable to damage.  

In the research team’s animal models, this resulted in muscle weakness, decreased motor function and other symptoms associated with multiple sclerosis. 

Identifying the executioner protein offers a new bullseye for targeted multiple sclerosis therapies. Already, Shukla’s lab has demonstrated that necrosulfonamide, which inhibits the executioner protein, can preserve nerve function in animal models. 

“Our findings enhance our understanding of how viruses develop and offer potential avenues for mitigating viral-induced neuronal damage,” Shukla said. 

It’s not possible to eradicate herpes. But Shukla hopes further investigations can reduce its presence and boost public awareness of the connections between HSV-1 and neurodegenerative diseases. 

Additional UIC coauthors from the UIC Department of Ophthalmology and Visual Sciences are Ilina Bhattacharya, Rashmi Kadam, Tejabhiram Yadavalli, Chandrashekhar D. Patil, Hemant Borase, Ipsita Volety, Sergey Kalinin and Douglas L. Feinstein. This research was funded by the National Eye Institute of the National Institutes of Health.