Intracerebral recombinant HSV-1 vector does not reactivate latent HSV-1

Area of Science:

• Neurovirology
• Gene Therapy
• Oncolytic Viruses

Background:

• Herpes simplex virus type-1 (HSV-1) is explored for gene delivery in the central nervous system for treating neurological conditions like brain tumors.
• A significant concern is the potential for recombinant HSV-1 to reactivate latent wild-type HSV-1, possibly causing encephalitis, as many individuals harbor latent HSV-1.

Purpose of the Study:

• To assess the risk of recombinant HSV-1 reactivating latent wild-type HSV-1 in the nervous system.
• To evaluate this risk using established rat models of HSV-1 latency.

Main Methods:

• Two rat models were used: corneal scarification and intracerebral injection to establish HSV-1 latency.
• Following latency, the ICP6(-) strain hrR3 (a defective recombinant virus) was administered intracerebrally.
• Control groups received cadmium sulfate to induce latent virus reactivation. Viral shedding and reactivation in trigeminal ganglia, cortical tissue, and eyes were assessed using cell culture and RT-PCR.

Main Results:

• Cadmium sulfate treatment successfully reactivated latent wild-type HSV-1, confirming model efficacy.
• Intracerebral injection of the ICP6(-) strain hrR3 did not lead to the reactivation of latent wild-type HSV-1 in either the corneal or cerebral latency models.

Conclusions:

• Intracranial administration of partially defective recombinant HSV-1, such as hrR3, appears to pose a minimal risk of reactivating latent wild-type HSV-1 in sensory ganglia or the brain.
• These findings support the safety profile of using defective HSV-1 vectors for gene therapy in neurological applications.