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Updated: Aug 16, 2026
A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation
Published on: April 2, 2012
Evidence that spontaneous reactivation of herpes virus does not occur in mice
Bryan M Gebhardt1, William P Halford
1LSU Eye Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. bgebha@lsuhsc.edu
Background:
Some species, including humans and rabbits, exhibit periodic viral reactivation and shed infectious virus at the infected end organ. Mice may be an exception, because spontaneous shedding of infectious virus rarely, if ever, occurs. However, spontaneous molecular reactivation, i.e., the expression of a few viral genes and the synthesis of the viral glycoproteins coded for by these genes, has been reported. This finding has prompted the assumption that molecular reactivation is an indicator of reactivation and the production of infectious virus. The goal of this study was to differentiate between viral gene expression during latency and the episodic production of infectious virus in mice.
Results:
Viral reactivation and infection were not seen in herpes simplex virus type 1 (HSV-1) latent ganglion graft recipient BALB/c scid or immunocompetent BALB/c mice, which survived the 65-day observation period with no evidence of viral infection although the immunocompetent mice developed cellular and humoral immunity to HSV-1. In contrast, BALB/c scid recipients of ganglia containing reactivating virus invariably developed a local and, subsequently, systemic viral infection and died within 14 days. Immunocompetent BALB/c mice that received ganglion grafts containing reactivating virus survived the infection and became immune to the virus. Trigeminal ganglia removed from scid and immunocompetent recipient graft sites 5, 14, and 28 days after transplantation contained latent virus and viable neurons.
Conclusion:
The results suggest that, within the limits of detection of the experiments, spontaneous episodic production of immunogenic viral antigens but not of infectious virus occurs in mouse neural ganglia during latency.
Insights
Mice may not shed infectious herpes simplex virus (HSV-1) during latency. Studies show viral gene expression occurs, but not infectious virus production, in mouse neural ganglia.
Area of Science:
- Neurovirology
- Immunology
- Molecular Biology
Background:
- Viral reactivation and shedding of infectious virus are observed in species like humans and rabbits.
- Mice are considered an exception due to rare spontaneous shedding of infectious virus.
- Spontaneous molecular reactivation, indicated by viral gene expression, has been reported in mice, leading to assumptions about infectious virus production.
Purpose of the Study:
- To differentiate between viral gene expression during latency and the episodic production of infectious virus in mice.
- To investigate the occurrence of spontaneous viral reactivation in mouse neural ganglia.
Main Methods:
- Transplantation of herpes simplex virus type 1 (HSV-1) latent ganglion grafts into BALB/c scid and immunocompetent BALB/c mice.
- Monitoring of viral reactivation, infection, and survival rates in recipient mice over a 65-day period.
- Analysis of trigeminal ganglia from recipient mice for latent virus and viable neurons at various time points post-transplantation.
Main Results:
- No viral reactivation or infection was observed in HSV-1 latent ganglion graft recipient BALB/c scid or immunocompetent mice.
- Recipients of ganglia with reactivating virus developed local and systemic infections, leading to death in scid mice within 14 days.
- Immunocompetent mice receiving grafts with reactivating virus survived and developed immunity; their trigeminal ganglia harbored latent virus and viable neurons.
Conclusions:
- Spontaneous episodic production of immunogenic viral antigens, but not infectious virus, occurs in mouse neural ganglia during latency.
- Molecular reactivation in mice does not necessarily equate to the production of infectious virus.
- The study provides evidence against spontaneous shedding of infectious HSV-1 in mice during latency.
