The protective role of IFN-λ at the ocular mucosal surface during corneal HSV-1 infection

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B241
Abstract ID: 4575

Presenting Author:
Jiayi Ren , Graduate Research Assistant at Auburn University College of Veterinary Medicine

Abstract:

Herpes simplex virus-1 (HSV-1) is a highly prevalent human pathogen and successful neurotropic virus that undergoes life-long latency in the trigeminal ganglion (TG). The recurrent HSV-1 infection of the cornea causes herpetic stromal keratitis (HSK), the most common cause of infectious blindness in the Western world. The emergence of multi-drug (anti-viral/acyclovir) resistant HSV-1 strains is a major concern for treating latent and recurrent HSV-1 infections. Using a primary mouse model of ocular HSV-1 infection, we show that HSV-1 infection induces a dominant IFN-λ response compared with type I IFNs in the cornea. The topical recombinant IFN-l (rIFN-λ) treatment during the early viral replication phase reduced viral burden at the primary site of HSV-1 replication, neuronal spread, and HSV-1 levels in the TG, significantly suppressing HSK progression. Early rIFN-λ treatment reduced IL-6, IL-1β, and CXCL-1 production in the cornea and promoted neutrophil-mediated anti-viral effector responses. Further, we demonstrate that rIFN-λ significantly suppresses acyclovir-resistant HSV-1 replication in the epithelial cells compared to acyclovir alone treatment groups. Our data indicate that local delivery of IFN-λ-therapy at the corneal mucosal surface can promote endogenous anti-viral responses and represents a promising alternative therapeutic approach against recurrent corneal HSV-1 infection caused by multi-drug-resistant HSV-1 strains.