Loss of ICP22 in HSV-1 Elicits Immune Infiltration and Maintains Stromal Keratitis Despite Reduced Primary and Latent Virus Infectivity

Investigative Ophthalmology & Visual Science
Harry MatundanHomayon Ghiasi

Abstract

We previously have reported that ICP22, an immediate early gene of herpes simplex virus type 1 (HSV-1), binds to the CD80 promoter to suppress CD80 expression in antigen-presenting cells, leading to reduced T-cell function and protection. In contrast, overexpression of CD80 exacerbates corneal scarring (CS) in ocularly infected mice. In this study we tested the hypothesis that the absence of ICP22 could increase disease severity. To test our hypothesis, BALB/c mice were ocularly infected after corneal scarification with a recombinant HSV-1 lacking the ICP22 gene with its parental wild-type (WT) virus (KOS) as a control. Virus replication in the eye, CS, angiogenesis, latency, and reactivation between ICP22 null virus and WT KOS were determined. In addition, expression of IL-2, IL-4, IFN-γ, IFN-α, granzyme A, granzyme B, and perforin by CD4 and CD8 T cells in corneas of infected mice on days 3, 5, 7, 10, 14, 21, and 28 postinfection were determined by flow cytometry. We found similar levels of eye disease and angiogenesis in mice following corneal scarification and ocular infection with the ICP22 null virus or parental WT virus despite reduced virus replication in the eye and reduced latency and reactivation in mice ocularly inf...Continue Reading

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Citations

Jun 10, 2020·Investigative Ophthalmology & Visual Science·Satoshi HiroseHomayon Ghiasi
Dec 31, 2020·Viruses·Christos DogrammatzisMaria Kalamvoki
May 21, 2021·Frontiers in Immunology·Luisa F DuartePablo A González
Jun 25, 2021·Frontiers in Microbiology·Ying WuAnchun Cheng

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Methods Mentioned

BETA
FACS
PCR
transgenic
flow cytometry

Software Mentioned

GraphPad
TreeStar
BD FacsDiva
FlowJo

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