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Harry Matundan, Ujjaldeep Jaggi, Homayon Ghiasi; The role of CD80 and HSV-1 ICP22 interaction on HSV-1 pathogenicity and latency-reactivation in infected mice. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1667 – A0497.
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© ARVO (1962-2015); The Authors (2016-present)
Previously we have shown that CD80 and not CD86 is suppressed in the corneas of mice ocularly infected with wild type (WT) HSV-1. This suppression of CD80 was mediated by binding of HSV-1 ICP22 to CD80 promoter. In addition, we found that ocular infection of mice with a recombinant HSV-1 expressing CD80 virus exacerbated eye disease in infected mice. In the current study, we investigated if any specific region of ICP22 is involved with the suppression of CD80 by using recombinant viruses lacking ICP22 gene or lacking ICP22 binding site to CD80 promoter.
BALB/c mice were scarified and ocularly infected with 2x105 pfu/eye of a recombinant virus lacking ICP22 (D22) or lacking CD80 binding region (KOS-ICP22Δ40). Parental avirulent HSV-1 strain KOS (WT) was used as a control. Viral replication in the eye, corneal scarring, latency-reactivation, and exhaustion markers were determined in infected mice. Flow cytometry analysis was done to evaluate the expression of immune infiltrates into the cornea. CD80 promoter activity was monitored by luciferase assays after infection.
Luciferase analysis of D22 and KOS-ICP22Δ40 infected cells compared with WT virus shown that ICP22 is involved in down-regulation of CD80 promoter in vivo and in vitro. At a functional level, both D22 and KOS-ICP22Δ40 viruses enhanced levels of effector CD8 T cell population and affected infiltrates in cornea of infected mice in a time-dependent fashion compared to WT virus. Suppression of CD80 in DCs was blocked in the absence of ICP22. The absence of ICP22 binding to CD80 promoter using both D22 and KOS-ICP22Δ40 viruses increased eye disease but latency and reactivation were not affected compared with WT virus.
Our results suggest that inhibiting the binding of HSV-1 ICP22 to CD80 promoter leads to increased HSV-1 pathogenicity. This is of particular interest, because it indicates that the absence of ICP22 leads to increased CD80 and CD8 expression in the eye of infected mice resulting in more eye disease. Thus, our data signifies that HSV-1 uses CD80 suppression by ICP22 as a mechanism of immune escape in order to protect the host from increased pathology.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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