Study Finds HSV-1 Changes How Brain’s Immune Cells Respond to Infection

A virus responsible for cold sores may also alter how the brain’s immune cells function long after an infection has passed, according to a new study from the University of Colorado Anschutz.

Researchers found that herpes simplex virus type 1 (HSV-1), which infects more than 60% of people and remains in the body for life, can change the behavior of microglia, the brain’s resident immune cells. The findings, published in PLOS Pathogens, point to a possible connection between viral infection, chronic inflammation, and Alzheimer’s disease.

Using advanced molecular techniques, the team examined how individual brain cells responded to HSV-1 infection and where those changes occurred. Infection produced distinct populations of microglia dominated by interferon signaling, a powerful antiviral defense mechanism, while genes involved in the cells’ normal protective and maintenance functions became less active. These changes were concentrated in brain regions where the virus was detected, suggesting HSV-1 creates localized areas of heightened immune activity. The researchers also found changes in chromatin, which can affect how easily genes are turned on or off.

“Microglia act as both the brain’s security system and its maintenance crew,” said senior author Christy Niemeyer. “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.”

“What makes these findings particularly interesting is that the virus isn’t simply triggering inflammation,” Niemeyer said. “It’s changing the molecular programs that control how these immune cells function. An important question is whether these changes persist after infection.”

Though serious complications from HSV-1 are rare, growing evidence links the virus to the chronic inflammation that may trigger Alzheimer’s disease, and it remains unclear how the virus might trigger and sustain that inflammation. 

“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 Kimberley Bruce. “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.”

Niemeyer noted that Alzheimer’s disease is shaped by multiple genetic and environmental factors, and that understanding how a common virus changes the brain’s immune environment may help explain why some people are more vulnerable to neurodegeneration. The researchers next plan to investigate whether these immune changes persist after infection and how repeated viral reactivation may influence long-term brain health.