Nectin-1-specific entry of herpes simplex virus 1 is sufficient for infection of the cornea and viral spread to the trigeminal ganglia

PURPOSE Primary and recurrent infections of the cornea by herpes simplex virus 1 (HSV-1) are important causes of eye disease. Three unrelated classes of glycoprotein D receptors for HSV-1 entry into cells have been identified. This study was undertaken to uncover the relative significance of nectin-1 as an entry receptor in corneal infection and HSV-1 spread to the trigeminal ganglia (TG), a site important for HSV-1 latency and recurrent corneal infection. METHODS To assess the significance of nectin-1, a member of the immunoglobulin superfamily, in primary HSV-1 infection and spread to the TG, we used a murine model of corneal infection and a HSV-1 mutant, KOS(Rid1), which can only use nectin-1 for entry. Immunohistochemistry, real-time PCR, and plaque assays using HSV-1 infected tissues were performed. RESULTS We demonstrated that receptor usage by HSV-1 limited to nectin-1 does not significantly change the spread of HSV-1 in the corneal epithelium during primary infection. We also found that nectin-1-specific entry does not affect the capacity of the virus to spread to the TG from the cornea. CONCLUSIONS Our findings suggest that nectin-1 alone is sufficient for HSV-1 entry into the cornea and spread to the TG.