For many, the herpes virus is a pervasive pest that causes painful and unsightly blisters.
But the truth is far more concerning than any crusty cold sore.
Research shows the herpes simplex virus (HSV-1) can infect the brain and nervous system, where it’s been implicated in triggering Alzheimer’s disease, possibly even doubling your risk of dementia.
For a virus that plagues billions, it’s vital we learn more about how HSV-1 infection works, and scientists just figured out a new piece of the puzzle.
In a study in PLOS Pathogens, researchers found HSV-1 can basically reprogram immune cells called microglia in the brain, and the effects might help explain how the virus contributes to the inflammation seen in diseases of cognitive decline.
Microglia are specialized immune cells that continually monitor and maintain the brain by detecting threats, clearing out dead cells and damaged tissue, and pruning neuronal connections – but in the presence of the herpes virus, their ability to carry out healthy brain maintenance appears to be jeopardized.
“When HSV-1 enters the brain, these cells shift into emergency defense mode,” says neuroscientist Christy Niemeyer from the University of Colorado Anschutz.
“While this helps fight the virus, it may also compromise their ability to perform the everyday functions, even after the virus is gone.”
In experiments, researchers infected mice with HSV-1, then examined their brains six days later, using genetic analysis and imaging techniques to investigate the animals’ immune responses and to map where the virus was present.
The results showed the virus was confined to discrete spots in the brainstem, rather than spreading throughout it, and microglial activation markers were higher in regions of the brain found to contain the virus.
What’s more, activated microglia showed dramatically increased interferon signaling, in which the immune cells release proteins as chemical warning signs to other nearby cells.
Compared to animals given a mock treatment, the proportion of interferon-responsive microglia was over 30 times higher in mice infected with HSV-1, suggesting the warning system could have gone into overdrive.
But that’s not all. Affected cells also showed reduced expression of genes linked to normal brain maintenance, monitoring, and communication, suggesting a “redistribution of microglial identities” that could potentially have detrimental consequences for brain health.
“Collectively, the suppression of these factors could impair microglial phagocytosis, clearance of neurotoxic factors, and promote protein aggregation, contributing to increased risk of neurodegenerative disease following HSV-1 infection,” the researchers explain in their paper.
“What makes these findings particularly interesting is that the virus isn’t simply triggering inflammation,” Niemeyer says.
“It’s changing the molecular programs that control how these immune cells function. An important question is whether these changes persist after infection.”
For now, we don’t have the answer to that.
What we do have is evidence – if only in an animal model – that HSV-1 appears to override normal microglial function in a way that both promotes inflammation as a first-line response to the virus, while disrupting the immune cells’ abilities to take care of the brain.
“Downregulation of these pathways suggests that HSV-1 infection shifts microglia away from their homeostatic maintenance functions toward a highly specialized antiviral state,” the researchers explain.
“Loss of these homeostatic programs has been reported in multiple neurological disorders, including Alzheimer’s disease and multiple sclerosis, raising the possibility that viral infection may initiate microglial state transitions that resemble those observed in neurodegenerative conditions.”
It’s worth emphasizing again that so far, we’ve only seen this immune response demonstrated in a small number of mice, and the animals were euthanized as part of the experiment, so we don’t have proof that they would have gone on to develop neurodegeneration.
But if the same immune responses are taking place in humans infected with HSV-1, it’s possible we’ve identified a critical pathway that contributes to cognitive decline.
“Given the growing evidence linking HSV-1 to long-term neuroinflammatory phenotypes and Alzheimer’s disease pathology, it is critical to explore the durability of these microglial state transitions,” the researchers conclude.
“Our findings provide a mechanism linking acute viral infection to the long-term neuroinflammation that may precede neurological disease.”
The findings are reported in PLOS Pathogens.
This article was fact-checked by Rebecca Dyer and edited by Rebecca Dyer. While we pride ourselves on our process, we are only human. If you spot a mistake, please let us know.
