Type I Interferon Signaling Is Critical During the Innate Immune Response to HSV-1 Retinal Infection

Shan Fan, Jae Hyuk Yoo, Garam Park, Steven Yeh, Christopher D. Conrady

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Article number28
JournalInvestigative Ophthalmology and Visual Science
Volume63
Issue number13
DOIs
StatePublished - Dec 2022

Keywords

  • acute retinal necrosis
  • eye
  • infection
  • innate immunity
  • type I interferons

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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