Summary: A new study reveals that herpes simplex virus-1 (HSV-1), commonly known for causing cold sores, can travel through the nasal cavity directly to the brain, causing severe and lasting neurological symptoms. In animal experiments, nasal HSV-1 infection led to persistent neurological dysfunction, including anxiety and cognitive impairment.
The researchers identified heparanase, a cellular enzyme, as a critical factor in allowing HSV-1 to cause severe, lasting neurological damage. Blocking the activity of this enzyme significantly reduced neurological damage in infected animals, highlighting a possible therapeutic target.
Key Facts:
- Neurological Impact: Intranasal HSV-1 infections lead to lasting neurological and cognitive impairments.
- Role of Heparanase: This enzyme facilitates HSV-1-induced brain damage; blocking it reduces neurological consequences.
- Global Prevalence: Approximately two-thirds of the global population carries HSV-1, emphasizing the potential wide-reaching impact of these findings.
Source: University of Illinois
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,” Shukla said. “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.”
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.
Funding: The study was funded by grants from the National Institutes of Health.
About this neurology research news
Author: Brian Flood
Source: University of Illinois
Contact: Brian Flood – University of Illinois
Image: The image is credited to Neuroscience News
Original Research: Open access.
“HPSE-mediated proinflammatory signaling contributes to neurobehavioral deficits following intranasal HSV-1 infection” by Deepak Shukla et al. mBio
Abstract
HPSE-mediated proinflammatory signaling contributes to neurobehavioral deficits following intranasal HSV-1 infection
Herpes simplex virus-1 (HSV-1) is a neurotropic virus that can infect the brain, and an uncontrolled infection can lead to a range of diseases, including chronic nerve pain, encephalitis, and neurobehavioral abnormalities.
These outcomes are often severe and have lasting consequences, highlighting the need to identify host factors that contribute to disease severity.
In this study, we report that intranasal HSV-1 infection in murine model, which promotes viral dissemination into the brain, implicates the host protein heparanase (HPSE) as a key mediator of neuroinflammation.
Specifically, we observed that the HPSE activity during HSV-1 infection in naïve animals promotes the upregulation of proinflammatory cytokines, enhances microglial activity in the brain, and contributes to cognitive impairment, anxiety, and motor coordination deficits.
Such effects are significantly less detectable in heparanase deficient (Hpse−/−) mice. Additionally, we found that moderate activation of toll-like receptors (TLRs), particularly in Hpse+/+ mice, may contribute to the activation of the inflammasome pathway.
This, in turn, leads to the activation of caspase-1 (Casp1) and caspase-3 (Casp3), which may play a role in nerve function loss.
Our findings position HPSE as a potential therapeutic target for mitigating virus-induced neuroinflammation and neurobehavioral defects.
