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The development of an improved murine iontophoresis reactivation model for the study of HSV-1 latency
Abstract:
The present study reviews the development of an effective murine iontophoresis reactivation model for the study of HSV-1 latency. In a series of experiments, Balb C mice latently infected with HSV-1 McKrae strain were iontophoresed with epinephrine X 3 days (EPI X 3/ION) or 6-hydroxydopamine X 1 day followed by topical epinephrine (6-HD ION/EPI). Reactivation and recovery of latent HSV-1 was determined by daily ocular swabs, titration, and neutralization. Additional studies determined the effect of topical ocular steroids on viral recovery rate. The results demonstrated no recovery of McKrae strain in Balb C (0%) with EPI X 3/ION, and no enhancement with topical steroids. 6-HD ION/EPI demonstrated a low recovery rate in mice (8%). However, the recovery rate was significantly increased to 50% by the addition of topical steroids to form the 6-HD ION/EPI/STEROID model, a useful experimental tool. The substitution of a clinical isolate, W strain, for McKrae strain further improved the model. The results demonstrated that, following the acute infection in mice, W strain was associated with a significantly higher (P = .001) survival rate than McKrae strain (81% vs. 52%). There was no statistically significant difference between the two strains, W vs McKrae, in Balb C mice comparing keratitis, establishment of latency (by co-cultivation), spontaneous shedding rate, or induced ocular shedding following iontophoresis. The development of an effective murine iontophoresis model offers an economical method which is uniquely suited for immunological and genetic studies of HSV-1 latency.
Insights
This study developed a new mouse model for studying herpes simplex virus type 1 (HSV-1) latency using iontophoresis. The 6-HD ION/EPI/STEROID model with topical steroids significantly improved HSV-1 reactivation rates.
Area of Science:
- Virology
- Immunology
- Ophthalmology
Background:
- Herpes simplex virus type 1 (HSV-1) establishes lifelong latency in neurons.
- Reactivation of latent HSV-1 can cause significant ocular disease, such as herpetic keratitis.
- Effective experimental models are crucial for understanding HSV-1 latency and developing therapeutic strategies.
Purpose of the Study:
- To develop and validate an effective murine iontophoresis model for studying HSV-1 latency and reactivation.
- To evaluate different iontophoresis protocols and viral strains for optimizing HSV-1 recovery.
- To assess the impact of topical ocular steroids on HSV-1 reactivation.
Main Methods:
- Balb C mice latently infected with HSV-1 (McKrae strain) were subjected to iontophoresis with epinephrine (EPI X 3/ION) or 6-hydroxydopamine followed by epinephrine (6-HD ION/EPI).
- HSV-1 reactivation was quantified using daily ocular swabs, titration, and neutralization assays.
- The effect of topical ocular steroids was evaluated in conjunction with iontophoresis protocols.
- A clinical isolate (W strain) was compared to the McKrae strain for its impact on survival and latency establishment.
Main Results:
- The EPI X 3/ION protocol showed no HSV-1 recovery (0%) in Balb C mice, with no enhancement by topical steroids.
- The 6-HD ION/EPI protocol yielded a low recovery rate (8%), which significantly increased to 50% with the addition of topical steroids (6-HD ION/EPI/STEROID model).
- The W strain demonstrated a significantly higher survival rate (81%) compared to the McKrae strain (52%) after acute infection, but no significant differences were observed in keratitis, latency establishment, or shedding rates.
Conclusions:
- The developed 6-HD ION/EPI/STEROID murine iontophoresis model, particularly with the W strain, provides an effective and economical tool for studying HSV-1 latency and reactivation.
- This model is suitable for immunological and genetic investigations into HSV-1 latency.
- Topical steroids significantly enhance HSV-1 recovery in this iontophoresis model.