Summary: New research shows that herpes simplex virus type 1 (HSV-1), the virus most commonly associated with cold sores, can invade selective regions of the brain and may contribute to the development of neurodegenerative conditions. Detailed mapping of HSV-1’s route into the central nervous system reveals that the virus preferentially targets areas that regulate sleep, movement, mood, appetite, and hormonal balance.
The researchers also report that HSV-1 activates the brain’s resident immune cells, microglia, producing an inflammatory response that in some regions persists after the virus itself is no longer detectable. This prolonged, localized inflammation is a plausible mechanism by which a common viral infection could increase the risk of later neurological decline.
These findings improve understanding of how HSV-1 interacts with the brain and offer direction for future studies exploring whether antiviral or anti-inflammatory strategies could reduce long-term neurological risk. The work provides important clues about potential links between HSV-1 infection and diseases such as Alzheimer’s.
Key Facts:
- HSV-1 spreads to and concentrates in specific brain regions, including areas that influence mood and hormonal regulation.
- Exposure to HSV-1 triggers microglial activation, creating an inflammatory state within affected regions.
- Persistent inflammation following HSV-1 exposure is a potential contributor to neurological and neurodegenerative disorders.
Source: University of Colorado
Herpes simplex virus type 1 (HSV-1), the cause of common cold sores, can enter the central nervous system and shows preference for certain brain regions.
Published in the Journal of Virology, this study offers one of the first comprehensive maps of how HSV-1 infiltrates the brain and which neural structures are most susceptible during primary infection. The results clarify potential routes of invasion and highlight brain regions whose altered function could explain links between HSV-1 and later neurological disease.
“Although HSV-1 has been suggested as a factor in neurodegenerative diseases such as Alzheimer’s, the precise routes and brain targets of invasion were not well defined,” says Christy Niemeyer, PhD, assistant professor of neurology at the University of Colorado Anschutz Medical Campus and co-first and corresponding author of the study. “Determining how HSV-1 reaches the brain and which regions are vulnerable is essential to understanding how the virus could initiate or exacerbate disease.”
Using an experimental mouse model and intranasal inoculation to mimic natural infection, the investigators traced HSV-1 movement from the nasal and oral epithelium into the central nervous system. Their results indicate that the virus does not disperse randomly: it follows defined pathways, infecting specific cranial nerve nuclei and brainstem structures that control vital functions such as sleep and movement.
Notably, HSV-1 antigens were present in neuromodulatory centers that produce serotonin and norepinephrine, and in the hypothalamus, while key regions like the hippocampus and cortex were spared in this model. Niemeyer emphasizes that even without overt encephalitis, the presence of virus or virus-triggered immune activation can impair normal function in these regulatory centers.
The study also examined how microglia respond to HSV-1 across different brain regions. While microglial activation was widespread during infection, some areas exhibited persistent microglial inflammation after viral antigens were no longer detectable. Persistent activation of microglia can promote chronic inflammation, which is recognized as a risk factor for various neurological and neurodegenerative disorders.
“Characterizing region-specific microglial responses provides important insight into how an otherwise common virus could leave lasting impacts on brain health,” Niemeyer explains. “Chronic, localized inflammation may be a key mechanism linking viral exposure to long-term neurological outcomes.”
About this neurology research news
Author: Kelsea Pieters
Source: University of Colorado
Contact: Kelsea Pieters – University of Colorado
Image: Image credit to Neuroscience News
Original Research: Closed access. “Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity” by Christy Niemeyer et al., Journal of Virology.
Abstract
Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity
Herpes simplex virus type 1 (HSV-1) typically infects the oral and nasal mucosa and establishes latency in the trigeminal ganglion and other peripheral ganglia. However, HSV-1 can also infect and become latent within the central nervous system independently of trigeminal latency. Prior work has proposed two distinct routes into the CNS: via the trigeminal ganglion–brainstem connection and via the olfactory nerve, but the specific brain regions targeted during primary infection have not been comprehensively characterized.
This study examined the timing and pattern of HSV-1 spread through the olfactory epithelium and into the brain following intranasal inoculation in a C57BL/6 mouse model, alongside the corresponding macrophage and microglial responses. The authors observed an apical-to-basal progression of HSV-1 through the olfactory epithelium with an accompanying macrophage-driven inflammatory response. Subsequent infection involved a defined subset of brain regions connected to the trigeminal pathways in the brainstem and other cranial nerve nuclei, including vagus and hypoglossal nuclei.
Additional regions positive for HSV-1 antigens included the locus coeruleus, raphe nucleus and hypothalamus, while structures such as the hippocampus and cortex were spared in this model. Microglial activation varied substantially between regions. These findings illuminate the region-specific dissemination of HSV-1 within the CNS and provide mechanistic insight that may help link viral infection to neurological and neurodegenerative disease processes.