Herpes simplex virus latency after direct ganglion virus inoculation

Area of Science:

• Virology
• Neuroscience
• Immunology

Background:

• Herpes simplex virus (HSV) latency typically establishes in ganglion neurons after transport from peripheral infection sites.
• The mechanism of HSV entry into neurons and subsequent latency establishment remains incompletely understood.

Purpose of the Study:

• To investigate whether direct inoculation of HSV into ganglia can establish latency, bypassing peripheral infection routes.
• To develop and utilize a ganglion transplant model to study HSV latency mechanisms.
• To assess the role of HSV replication in the establishment of latency.

Main Methods:

• Direct surgical inoculation of HSV into mouse ganglia.
• Development of a mouse ganglion explant and transplantation model for HSV inoculation.
• Evaluation of latency markers including latency-associated transcript (LAT) expression, viral RNA (ICP4), viral antigen, and viral isolation.
• Assessment of antiviral drug effects on HSV replication and latency in the transplant model.

Main Results:

• Direct HSV inoculation of ganglia led to latency-associated transcript (LAT) expression, indicating successful latency establishment.
• Transplanted ganglia, inoculated with HSV, showed evidence of latency: LAT presence, absence of ICP4 RNA/antigen, and recoverable virus from explants but not homogenates.
• Inhibition of HSV replication with antivirals significantly reduced the number of LAT-positive neurons in transplanted ganglia.

Conclusions:

• Direct inoculation of ganglia can establish HSV latency, independent of peripheral infection routes.
• HSV replication plays a critical role in the establishment of latency within ganglion neurons.
• The developed direct inoculation and transplant models offer novel approaches for studying HSV latency mechanisms.