HSV-1 Can Cause Long-Term Brain Damage

Herpes simplex virus-1 (HSV-1) is widely recognized for causing oral blisters, but research suggests it can also affect the nervous system, leading to severe neurological symptoms. A new study from the University of Illinois Chicago (UIC) finds that when HSV-1 enters the body through the nose, it can trigger long-term cognitive and motor impairments, along with heightened anxiety-related behaviors.

Published in mBio, the study is the first to demonstrate that HSV-1 exploits a cellular enzyme to drive neurological damage, highlighting the potential consequences of viral infections beyond their immediate symptoms.

A direct route to the brain

HSV-1 is typically transmitted through direct contact with saliva or infected surfaces, often resulting in cold sores. However, previous studies have shown that the virus can also travel to the eye and brain, where it may contribute to conditions like encephalitis and blindness. The new study focused on intranasal infection, a less-explored pathway that provides more direct access to the nervous system.

The researchers found that when HSV-1 was introduced through the nasal cavity in animal models, it rapidly spread to the brain, triggering inflammation and neuronal damage within days. The effects persisted for several months – equivalent to decades in a human lifespan – leading to reduced motor coordination, impaired memory and increased anxiety-like behaviors compared to uninfected controls.

“There is definitely nerve damage if you take the intranasal route, and the effects are long-term, which is alarming,” said Deepak Shukla, professor of microbiology and immunology at UIC and senior author of the study.

A key enzyme in viral damage

The study also identified heparanase, a cellular enzyme, as a key player in HSV-1’s ability to cause neurobehavioral deficits. Previous research from Shukla’s group had implicated heparanase in HSV-1 reinfection and persistence, but this study is the first to link it to long-term brain dysfunction.

Animals with a deactivated heparanase gene did not show the same neurological impairments after HSV-1 infection as those with normal enzyme activity. This suggests that heparanase contributes to viral spread and inflammation in the brain, making it a potential target for therapeutic interventions.

“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.

Implications for global health

HSV-1 is one of the most common viral infections worldwide, with the World Health Organization estimating that nearly two-thirds of the global population carry the virus. While most individuals experience mild symptoms, this study underscores the importance of understanding potential long-term neurological risks, particularly for individuals with frequent viral reactivation.

“The virus reactivates throughout life; it’s a lifelong infection,” said Chandrashekhar Patil, research assistant professor at UIC and co-author of the study. “So, I think this awareness will be really important among the large population which is carrying this virus.”

Reference: Borase H, Patil CD, Valyi-Nagy T, Shukla D. HPSE-mediated proinflammatory signaling contributes to neurobehavioral deficits following intranasal HSV-1 infection. Zhao L, ed. mBio. 2025:e03765-24. doi: 10.1128/mbio.03765-24

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