Olfactory and Trigeminal Routes of HSV-1 CNS Infection with Regional Microglial Heterogeneity

Area of Science:

• Neurovirology
• Immunology
• Infectious Diseases

Background:

• Herpes simplex virus type 1 (HSV-1) establishes latency in peripheral ganglia and can infect the central nervous system (CNS).
• HSV-1 CNS entry routes include the trigeminal nerve and olfactory nerve.
• Limited understanding exists regarding HSV-1's primary infection sites within the CNS and region-specific microglial responses.

Purpose of the Study:

• To investigate the temporal and spatial dissemination of HSV-1 within the CNS after intranasal inoculation.
• To characterize the region-specific immune response by microglia and macrophages during HSV-1 infection.
• To identify brain regions vulnerable to HSV-1 entry and spread.

Main Methods:

• Intranasal inoculation of HSV-1 in a C57BL/6 mouse model.
• Time-course analysis of viral spread within the olfactory epithelium (OE) and CNS.
• Assessment of macrophage and microglial activation in different brain regions.

Main Results:

• HSV-1 spread from the apical to basal olfactory epithelium, followed by infection of specific brainstem nuclei and cranial nerve nuclei.
• HSV-1 antigens were detected in the locus coeruleus, raphe nucleus, and hypothalamus, sparing the hippocampus and cortex.
• Microglial activation varied significantly across brain regions, with some showing sustained activation independent of viral presence.

Conclusions:

• HSV-1 disseminates through distinct anatomical pathways within the CNS following intranasal infection.
• Region-specific microglial responses correlate with viral presence and may influence disease pathogenesis.
• Findings provide insights into HSV-1's role in neurological diseases and neurodegeneration.