Herpes simplex virus type 1 (HSV-1), the virus that causes cold sores, reshapes microglia in a narrow region of the brainstem, according to new research led by the University of Colorado Anschutz; whether the changes last, or matter for Alzheimer’s risk, is unknown.
Micrograph of a herpes simplex virus. Image credit: CDC / Erskine Palmer.
HSV-1 infects a large share of the world’s population and lies dormant in nerve cells for life.
Although serious complications are rare, growing evidence links HSV-1 to the chronic inflammation that may trigger Alzheimer’s disease.
However, it is not clear how the virus may trigger and maintain this inflammation.
“Microglia act as both the brain’s security system and its maintenance crew,” said University of Colorado Anschutz’s Dr. Christy Niemeyer, co-senior author of the study.
“When HSV-1 enters the brain, these cells shift into emergency defense mode.”
“While this helps fight the virus, it may also compromise their ability to perform the everyday functions, even after the virus is gone.”
In the study, the researchers infected mice with a strain of HSV-1, then examined their brains six days later, at what they describe as the peak of the innate immune response.
Using advanced molecular techniques, they examined how individual brain cells responded to HSV-1 infection and where these changes occurred.
They discovered that infection produced distinct populations of microglia dominated by interferon signaling, a powerful antiviral defense mechanism.
At the same time, genes involved in the cells’ normal protective and maintenance functions became less active.
Importantly, these changes were concentrated in brain regions where the virus was detected, suggesting that HSV-1 creates localized areas of heightened immune activity.
The scientists also found changes in chromatin, the material that packages DNA inside cells. These changes can affect how easily genes are turned on or off.
“Interestingly, the way that HSV-1 finely tunes the immune response in microglia, resemble patterns found in response to other factors that drive Alzheimer’s disease,” said co-senior author Dr. Kimberley Bruce, also from the University of Colorado Anschutz.
“Although we have not established that HSV-1 causes Alzheimer’s, it highlights the immune programming of microglia as a common factor linking infection, aging and genetic risk factors.”
“Alzheimer’s disease is influenced by multiple genetic and environmental factors,” Dr. Niemeyer said.
“Understanding how a common virus changes the brain’s immune environment may help us identify why some individuals become more vulnerable to neurodegeneration.”
The study was published online in the journal PLoS Pathogens.
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S. Frietze et al. 2026. Intranasal HSV‑1 infection drives region‑specific interferon‑dominant microglial remodeling. PLoS Pathog 22 (10): e1014684; doi: 10.1371/journal.ppat.1014684
