Changes in Corneal Innervation after HSV-1 Latency Established with Different Reactivation Phenotypes

Area of Science:

• Ophthalmology
• Virology
• Neuroscience

Background:

• Herpes simplex virus 1 (HSV-1) is a common cause of infectious blindness.
• Corneal HSV-1 infection can lead to persistent nerve damage and vision impairment.

Purpose of the Study:

• To investigate the long-term effects of HSV-1 infection on corneal innervation in a rabbit model.
• To evaluate the role of specific HSV-1 genes, glycoprotein K (gK) and infected cell protein 0 (ICP0), in corneal nerve damage.

Main Methods:

• Rabbits were infected with wild-type HSV-1 strains (McRae, 17Syn+) or recombinant HSV-1 mutants lacking gK or ICP0.
• Corneal innervation was assessed at 124-125 days post-infection using immunofluorescence staining for βIII tubulin.
• Sub-basal nerve density and stromal nerve integrity were quantified and compared between infected and control groups.

Main Results:

• HSV-1 infection caused significant damage to both epithelial and stromal nerves in rabbit corneas.
• Infection with wild-type strains (McRae, 17Syn+) resulted in severe nerve destruction and scarring.
• Mutants with gK or ICP0 deletions showed attenuated nerve damage, with reduced sub-basal nerve loss and preserved stromal networks.

Conclusions:

• Primary HSV-1 corneal infection induces persistent, severe corneal nerve damage.
• Reducing viral replication (ICP0 deletion) or axonal transport (gK deletion) significantly mitigates HSV-1-induced corneal nerve pathology.