Herpes infection through the nose can lead to anxiety, motor impairment and cognitive deficits

Herpes simplex virus-1 (HSV-1) is commonly known for causing blisters and sores. But in some cases, the virus can migrate to the eye or nervous system, causing severe, chronic symptoms.

Now, a study from University of Illinois Chicago researchers finds that herpes infection through the nose can lead to anxiety, motor impairment and cognitive issues. The research is the first to show that, by exploiting a cellular enzyme, the virus can produce behavioral symptoms. The finding emphasizes the need for prevention and treatment of a virus carried by billions of people worldwide. 

The research, published in mBio, is the latest from the College of Medicine group led by Deepak Shukla, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye and UIC professor of microbiology and immunology.

Shukla's laboratory previously studied how the virus spreads to the eye and brain and can lead to blindness, encephalitis and other conditions. The new research looked at intranasal infection, where viral particles enter the body through the nose and have more direct access to the nervous system. 

If an infected individual is shedding virus via tears, it could reach the nasal cavity, where it could go more directly to the brain. I think it's underdiagnosed and understudied, but the neurological consequences, we believe, are much more severe than you would normally see with fever blisters or ocular infection." 

Deepak Shukla, the Marion H. Schenk Esq. Professor in Ophthalmology for Research of the Aging Eye and UIC professor of microbiology and immunology

In animal experiments, the researchers observed high levels of inflammation and neuronal damage just days after HSV-1 infection. For several months after - equivalent to decades of life in humans - infected animals performed more poorly on tests of motor coordination and memory and exhibited more anxiety-like behavior when compared to controls.

"There is definitely nerve damage if you take the intranasal route, and the effects are long-term, which is alarming," Shukla said. 

The researchers also studied heparanase, a cellular enzyme the group previously studied for its role in HSV-1 reinfection and long-term effects. Animals with a deactivated gene for heparanase did not show the same neurobehavioral deficits after infection as control animals. That suggests the enzyme mediates some of the virus' damaging effects in the brain. 

"These insights open the door to potential therapeutic approaches to mitigate the effects of neuroinflammation and prevent long-term brain injury caused by viral infections," said Hemant Borase, a UIC postdoctoral researcher and first author of the study. 

Herpes simplex virus-1 is extremely common. The World Health Organization estimates that nearly two-thirds of the global population carry the virus. 

"The virus reactivates throughout life; it's a lifelong infection" said Chandrashekhar Patil, research assistant professor in the College of Medicine and co-author of the paper. "So, I think this awareness will be really important among the large population which is carrying this virus." 

Tibor Valyi-Nagy, professor of pathology, is also a co-author of the paper. The study was funded by grants from the National Institutes of Health.