Neuronal Subtype Determines Herpes Simplex Virus 1 Latency-Associated-Transcript Promoter Activity during Latency.

Area of Science:

• Neurovirology
• Cellular Neuroscience

Background:

• Herpes simplex virus (HSV) establishes lifelong latency in neurons, a process not fully understood due to neuronal heterogeneity.
• Understanding neuronal subtypes involved in HSV latency is crucial for mechanistic studies.

Purpose of the Study:

• To investigate the role of specific sensory neuron subtypes in the establishment and maintenance of HSV latency.
• To explore the differential expression of latency-associated transcripts (LATs) in various neuronal populations.

Main Methods:

• Utilized primary cultures of adult mouse trigeminal ganglion (TG) neurons in microfluidic devices.
• Employed an in vivo model to study HSV-1 infection and latency in sensory neurons.
• Analyzed HSV-1 infection kinetics, LAT promoter activity, and early reactivation in different neuronal subtypes.

Main Results:

• HSV-infected neurofilament heavy-positive (NefH+) neurons exhibited higher LAT expression compared to NefH- neurons.
• Differential infection kinetics, including viral particle transport to the cell body, were observed between neuronal subtypes.
• A specific subset, NefH+ calcitonin gene-related peptide α (CGRP+) neurons, showed the highest LAT promoter activity and were involved in early HSV-1 reactivation.

Conclusions:

• Sensory neurons expressing neurofilaments (NefH+) demonstrate enhanced LAT promoter activity, suggesting a role in efficient HSV latency.
• Neuronal subtype is a critical determinant of HSV-1 infection outcome and latency establishment.
• Hypothesize that slower early HSV-1 invasion in NefH+ neurons may facilitate latency establishment by allowing antiviral responses to precede viral arrival at the cell body.