Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection
Year: 2022
Type: article
Abstract: Purpose: Acute retinal necrosis (ARN) is a herpesvirus infection of the retina with blinding complications. In this study, we sought to create a reproducible mouse model of ARN that mimics human disease to better understand innate immunity within the retina during virus infection. Methods: C57Bl/6J wild type (WT) and type I interferon receptor-deficient (IFNAR-/-) mice were infected with varying amounts of herpes simplex virus type 1 (HSV-1) via subretinal injection. Viral titers, optical coherence tomography (OCT) and fundus photography, the development of encephalitis, and ocular histopathology were scored and compared between groups of WT and IFNAR-/- mice. Results: The retina of WT mice could be readily infected with HSV-1 via subretinal injection resulting in retinal whitening and full-thickness necrosis as determined by in vivo imaging and histopathology. In IFNAR-/- mice, HSV-1-induced retinal pathology was significantly worse when compared with WT mice, and viral titers were significantly elevated within two days after infection and persisted to day 5 after infection within the retina. These results were also observed in the brain where there were significantly higher viral titers and frequency of encephalitis in IFNAR-/- when compared to WT mice. Conclusions: Collectively, these findings show that our new mouse model of ARN mimics human disease and can be used to study innate immunity within the retina. We conclude that type I interferons are critical in containing HSV-1 locally within retinal tissues and prohibiting spread into the brain.
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,850
Funder: National Eye Institute
OpenAlex ID: W4313364718