Herpes simplex virus type 1 (HSV-1), the virus responsible for cold sores, alters populations of microglia in small areas of the brainstem, according to a study led by researchers at the University of Colorado Anschutz College. The researchers found localized, interferon-dominated immune changes in infected mice, but it remains unknown whether these changes persist or influence the risk of Alzheimer’s disease.
HSV-1 infects a large proportion of the world’s population and remains dormant in nerve cells for life. Although serious complications are rare, growing evidence has linked HSV-1 with the chronic inflammation associated with Alzheimer’s disease. However, it is not clear how the virus initiates or maintains this inflammation.
Microglia respond to infection
“Microglia serve as both the brain’s security system and its maintenance personnel,” said study co-senior author Kristy Niemeyer, Ph.D., of the University of Colorado Anschutz College.
“When HSV-1 enters the brain, these cells go into emergency defense mode.”
“This helps fight the virus, but it can also impair the ability to function in daily life even after the virus is gone.”
For the study, the researchers infected mice with an HSV-1 strain and examined their brains six days later, when the innate immune response is thought to be at its peak. They used advanced molecular techniques to analyze how individual brain cells responded to the infection and where those changes occurred.
The infection produced distinct populations of microglia dominated by interferon signaling, a powerful antiviral defense mechanism. At the same time, the activity of genes involved in the cells’ normal protective and maintenance functions declined.
The changes were concentrated in brain regions where the virus was detected, suggesting that HSV-1 produces localized areas of heightened immune activation.
Changes to gene regulation
The researchers also identified changes in chromatin, the material that packages DNA inside cells. Such changes can affect how easily genes are switched on or off.
“Interestingly, the way HSV-1 fine-tunes the microglial immune response is similar to patterns seen in response to other factors that cause Alzheimer’s disease,” said co-author Kimberly Bruce, Ph.D., also of the University of Colorado Anschutz College.
“While HSV-1 has not been proven to cause Alzheimer’s disease, this study highlights the microglial immune program as a common factor linking infection, aging, and genetic risk factors.”
“Alzheimer’s disease is influenced by multiple genetic and environmental factors,” Niemeyer said. “Understanding how common viruses alter the brain’s immune environment may help identify why some people are more vulnerable to neurodegeneration.”
Study publication
The study was published online in PLoS Pathogens. The paper is available through the journal.
S. Frietze et al. 2026. “Intranasal HSV-1 infection promotes region-specific interferon-dominated microglial remodeling.” PLoS Pathogens 22 (10): e1014684. doi: 10.1371/journal.ppat.1014684.
Source: www.sci.news
