Stacking the odds: Multiple sites for HSV-1 latency.

Area of Science:

• Virology
• Immunology
• Neuroscience

Background:

• Herpes simplex virus (HSV) establishes lifelong latency, primarily in sensory neurons.
• The latency-associated transcript (LAT) is the only known abundant viral gene during HSV latency in neurons.
• The cellular reservoirs for HSV latency beyond neurons remain largely unexplored.

Purpose of the Study:

• To investigate the presence and distribution of HSV-1 latency-associated transcripts (LAT) in diverse cell types within the trigeminal ganglia (TG) of latently infected mice.
• To determine if non-neuronal cells contribute to HSV-1 latency.
• To understand the cellular landscape of HSV-1 quiescent infection.

Main Methods:

• Isolation of various cell types (B cells, dendritic cells, fibroblasts, glial cells, innate lymphoid cells, macrophages, microglia, monocytes, natural killer cells, neurons, neutrophils, and T cells) from TG of latently infected mice.
• Detection and quantification of LAT expression in these isolated cell populations.
• Comparative analysis of LAT presence across different cell types.

Main Results:

• LAT was detected in all investigated cell types isolated from the TG.
• Dendritic cells (DCs), neurons, and innate lymphoid cells (ILCs) exhibited the highest proportion of LAT-positive cells.
• These findings indicate a broader cellular distribution of HSV-1 latency than previously recognized.

Conclusions:

• HSV-1 can establish quiescent/latent infections in a variety of non-neuronal cell types within the TG.
• The presence of LAT in multiple cell types expands our understanding of HSV-1 latency reservoirs.
• This broader cellular involvement may enhance the survival and persistence of HSV-1 within the host.